Молекулярные механизмы, ограничивающие пролиферативный эффект индивидуальных факторов роста одним клеточным циклом тема диссертации и автореферата по ВАК РФ 03.00.03, кандидат биологических наук Андреева, Виктория Викторовна

• Андреева, Виктория Викторовна
• кандидат биологических наук
• 2004

Оглавление диссертации кандидат биологических наук Андреева, Виктория Викторовна

Список сокращений

ВВЕДЕНИЕ

ОБЗОР ЛИТЕРАТУРЫ

1 .Клеточный цикл

1.1 Универсальная теория клеточного цикла

1.2 Белковые регуляторы клеточного цикла

1.2.1 Белки семейства Rb

1.2.2 Комплексы Cdk/циклин в середине G1 периода

1.2.3 Комплексы Cdk/циклин в позднем G1 периоде

1.2.4 Комплексы Cdk/циклин в S и G2 фазах

1.2.5 Семейство Cdk ингибиторов INK

1.2.6 Семейство Cdk ингибиторов CIP/KIP 1 б

2. Факторы роста

2.1. Факторы роста фибробластов

2.1.1. Структура, регуляция синтеза и внутриклеточная локализация FGF

2.1.2. Рецепторы FGF и HSPG

2.2. Тромбоцитарный фактор роста

2.2.1. Структура и регуляция биосинтеза PDGF

2.2.2. Семейство рецепторов PDGF

2.3. Сыворотка крови

2.4. Активация тирозинкиназных рецепторов факторами роста

3. Пролиферативное старение и покой

3.1. Пролиферативный покой

3.2. Пролиферативное старение 32 МАТЕРИАЛЫ И МЕТОДЫ 35 Клеточные культуры и условия культивирования клеток 35 Перевод клеток в состояние пролиферативпого покоя 36 Факторы роста 36 Приготовление радиоавтографических препаратов 37 Анализ препаратов, меченных Н-тимидином 37 Построение кривых роста 38 Получение белковых лизатов 38 Иммунопреципитация 38 Иммуиоблоттинг 39 Определение киназпой активности комплекса Cdk2AmiamH Е

Иммуноистощение р21 и р

Выделение РНК и Норзерн блот

Инфекция клеток Swiss ЗТЗ аденовирусом, кодирующим циклин А или GFP

Получение клонов, экспрессирующих антисмысловую РНК р

Иммунофлуоресцентная конфокальная микроскопия

Проточная цитометрия

РЕЗУЛЬТАТЫ

1. Пролиферативный эффект FGF-1 и PDGF-AB на клетки Swiss ЗТЗ

2. Определение способности клеток Swiss ЗТЗ проходить более одного клеточного цикла при их стимуляции FGF-1 и PDGF-AB

3. Динамика вступления в репликацию клеток Swiss ЗТЗ, стимулированных сывороткой после длительной стимуляциии FGF

4. Митогенный ответ клеток Swiss ЗТЗ на сыворотку после длительной стимуляции FGF-1 и PDGF-AB

5. Молекулярно-биологическое исследование пролиферативного состояния клеток, находящихся в первом и во втором клеточном циклах после их стимуляции FGF-1 и PDGF-AB

5.1 Уровень фосфорилирования рецепторов FGF и PDGF

5.2 Уровень фосфорилирования МАРК

5.3 Сравнение экспрессии генов раннего и задержанного ответа

5.4 Экспрессия циклинов и циклинзависимых киназ

5.5 Экспрессия ингибиторов Cdk

5.6 Уровень циклинов в стареющей культуре HUVEC

6. Сравнение митогенного ответа на факторы роста в стареющих культурах фибробластов мышей SAMP-1 и SAMR

7. Искуственная экспрессия циклина А не вызывает вступления во второй клеточный цикл клеток Swiss ЗТЗ, стимулированиых FGF

8. Внутриклеточное распределение р21 и р27 в клетках Swiss ЗТЗ, стимулированных FGF-1, PDGF-AB или сывороткой

9. В клетках, стимулированных FGF-1 и PDGF-AB, р21 и р27 связаны с комплексом Сс1к2/циклин Е во втором клеточном цикле

10. Снижение активности комплекса Сс1к2/циклин Е во втором клеточном цикле после стимуляции клеток FGF-1 и PDGF-AB

11. Влияние экспрессии антисмысловой РНК р21 (as р21) на вхождение клеток во второй цикл после стимуляции FGF

ОБСУЖДЕНИЕ РЕЗУЛЬТАТОВ выводы

Введение диссертации (часть автореферата) на тему «Молекулярные механизмы, ограничивающие пролиферативный эффект индивидуальных факторов роста одним клеточным циклом»

За последние три десятилетия описано множество полипептидных факторов роста (ПФР), а также накоплено огромное количесто данных о механизмах их действия. ПФР являются регуляторами клеточных функций, включая пролиферацию, миграцию, дифференцировку и выживание/апоптоз. Стимуляция клеток ПФР является сложным процессом, заключающимся в передаче внеклеточного сигнала внутрь клетки. Ключевое событие этого процесса - это связывание фактора роста со специфическим рецептором, находящимся на поверхности клетки, что приводит к активации сигнальиых каскадов, которые достигают ядра и вызвают транскрипцию белковых факторов, управляющих пролиферацией и дифференцировкой, или напрямую влияют на функции клеточных белков, таких как ферменты и белки цитоскелета.

Большинство исследований молекулярных механизмов действия ПФР ограничивается лишь кратковременной стимуляцией клеток. Однако, изучение биохимического состояния клеток при длительной стимуляции ПФР представляет практическое значение в связи с увеличивающимся интересом к применению факторов роста в клинике, например при лечении ран и хронических язв, регенерации кровеносных сосудов и сердечной мышцы (Waltenberger, 1997; Kunimoto, 1999; Limat and French, 1999; Payne et al., 2001; Heilmann et al., 2002).

Неисследованным остается обнаруженный более 20 лет назад парадокс: с одной стороны, ПФР способны вызывать вступление в S период клеток, находящихся в состоянии пролиферативного покоя, с другой стороны, они обычно не способны поддерживать постоянную пролиферацию клеток в культуре, когда применяются индивидуально.

Таким образом, несмотря на накопленные впечатляющие знания о ростовых факторах, множество аспектов механизмов их действия все еще остаются пе исследованными.

Цели и задачи исследования. Целью настоящей работы являлось изучение длительного воздействия ПФР, в частности FGF-1 и PDGF-AB, на пролиферацию клеток. В качестве модели нормальных нетрансформированных клеток были выбраны фибробласты линии Swiss ЗТЗ.

В ходе работы предстояло решить две основные задачи:

1. определить на каком этапе происходит остановка пролиферации клеток при длительной стимуляции FGF-1 и PDGF-AB;

2. охарактеризовать состояние клеток при длительной стимуляции FGF-1 и PDGF-AB, а именно:

2.1. определить фосфорилирование рецепторов FGF и PDGF;

2.2. исследовать активацию MAP киназ;

2.3. исследовать индукцию генов раннего и задержанного ответов;

2.4. проверить уровень циклинзависимых кииаз (Cdk) и циклинов;

2.5. определить уровень ингибиторов Cdk и их внутриклеточную локализацию.

Научная новизна и практическая значимость. В настоящей работе было исследовано влияние продолжительной стимуляции FGF-1 и PDGF-AB на пролиферацию клеток Swiss ЗТЗ. Впервые было показано, что блок пролиферации при стимуляции клеток Swiss ЗТЗ FGF-1 и PDGF-AB происходит в G1 периоде второго клеточного цикла.

В работе биохимически охарактеризовано состояние клеток после блока пролиферации во втором цикле при их стимуляции FGF-1 и PDGF-AB. Показано, что рецепторы FGF (FGFR1) и PDGF-AB (PDGFRP) остаются фосфорилированными во втором цикле, так же как и MAP киназы Erkl и Erk2, проводящие пролиферативный сигнал в клеточные ядра. Во втором цикле при стимуляции клеток FGF-1 наблюдается экспрессия м-РНК генов раннего (c-jun, c-myc) и задержанного (ODC) ответов.

Показано, что в клетках, блокированных во втором клеточном цикле при их стимуляции FGF-1 и PDGF-AB, выражена экспрессия циклинов D1 и Е, но отсутствует экспрессия циклина А. Искусственная экспрессия циклина А не приводит к увеличению доли клеток, вступающих во второй цикл при стимуляции FGF-1.

В работе также показано, что в клетках, стимулированных FGF-1, значительно повышена экспрессия ингибитора Cdk, р21, в то время как при стимуляции PDGF-AB в клетках наблюдается аккумуляция р27. р21 и р27 находятся в комплексе Cdk2AiHiamH Е при стимуляции клеток соответственно FGF-1 или PDGF-AB и ингибируют активность этого комплекса во втором цикле. Используя антисмысловую м-РНК р21, показано, что повышенная экспрессия р21 является одной из причин, блокирующих пролиферацию клеток Swiss ЗТЗ при стимуляции FGF-1.

Научно-практическое значение работы состоит в том, что в ней получены новые данные, демонстрирующие ограниченность пролиферативного эффекта индивидуальных ПФР одним клеточным циклом и проливающие свет на биохимические механизмы, определяющие эту ограниченность. На основе полученных в данной работе результатов можно предположить, что большинство клеток при стимуляции индивидуальными ПФР задерживается во втором клеточном цикле. Дальнейшее исследование механизмов задержки во втором цикле должно способствовать разработке новых подходов к предотвращению гиперплазии и опухолеобразования, а также усовершенствованию методов применения ростовых факторов в клинике.

ОБЗОР ЛИТЕРАТУРЫ

Заключение диссертации по теме «Молекулярная биология», Андреева, Виктория Викторовна

выводы

1 Исследованы пролиферативпые эффекты FGF-1 и PDGF-AB на пролиферацию клеток Swiss ЗТЗ. Показано, что FGF-1 и PDGF-AB способны вызывать вхождение клеток Swiss ЗТЗ в S фазу и митоз, но неспособны поддерживать их продолжительную пролиферацию. Используя метод двойного изотопного мечения, установлено, что остановка клеток Swiss ЗТЗ при стимуляции FGF-1 и PDGF-AB происходит во втором клеточном цикле.

2 Показано, что клеткам, культивированным в присутствии FGF-1 в течение двух суток, требуется 12-14 ч для вхождения в S период после стимуляции сывороткой, как и клеткам, находящимся в состоянии пролиферативного покоя в результате сывороточного голодания.

3 Установлено, что сигнальные пути от FGFR и PDGFR остаются активными во втором клеточном цикле. В частности, FGFR и PDGFR остаются фосфорилированными во втором клеточном цикле при стимуляции клеток соответственно FGF-1 и PDGF-AB. МАРК (Erkl и Erk2) фосфорилированы как в первом, так и во втором цикле при стимуляции клеток FGF-1, PDGF-AB и сывороткой. Клетки, стимулированные FGF-1, отличаются повышенной экспрессией м-РНК генов раннего (c-jun) и задержанного (ОДС) ответа в первом и втором цикле.

4 Показано,что уровень циклина D1 и циклина Е не изменяется во втором цикле по сравнению с первым циклом при стимуляции клеток FGF-1, PDGF-AB и сывороткой. В клетках, стимулированных FGF-1 и PDGF-AB, происходит резкое снижение содержания циклииа А во втором цикле. Однако исскуственная экспрессия циклина А в клетках, стимулированных FGF-1, не повышает вероятности их вхождения во второй цикл.

5 Обнаружено, что в стареющих клетках характер экспрессии циклинов сходен с таковым в клетках, задержанных во втором цикле. В то же время, стареющие клетки, в том числе полученные из ускоренно стареющих животных, неспособны отвечать синтезом ДНК на стимуляцию сывороткой.

6 Показано, что уровень р21 значительно повышен в клетках, стимулированных FGF-1, как в первом так и во втором клеточном цикле, в то время как в клетках, стимулированных PDGF-AB, происходит повышение уровня р27 во втором цикле. Во втором цикле происходит аккумуляция р21 и р27 в ядрах клеток, стимулированных соответсвенно FGF-1 и PDGF-AB.

7 Во втором цикле происходит резкое усиление связывания комплекса Сс1к2/циклин Е с р21 после стимуляции клеток FGF-1. Аналогичные результаты по связыванию р27 с комплексом С<3к2/циклин Е получены для клеток, стимулированных PDGF-AB. Одновременно наблюдалось снижение активности комплекса Сс1к2/циклин Е во втором цикле после стимуляции клеток FGF-1 или PDGF-AB

Показано, что р21 частично ответственен за подавление репликации во втором клеточном цикле. Экспрессия антисмысловой м-РНК р21 в клетках, стимулированных FGF-1, приводит к увеличению доли клеток, входящих во второй цикл.

Список литературы диссертационного исследования кандидат биологических наук Андреева, Виктория Викторовна, 2004 год

1. Епифанова О.И., Терских В.В., Полуновский В.А. Покоящиеся клетки. Свойства и функции в организме. М.: Наука. 1983.

2. Оловников A.M. Принцип маргинотомии в матричном синтезе полинуклеотидов. 1971, Доклады Академии Наук, т. 201, с. 1496-1499.

3. Acland, P., М. Dixon, G. Peters and С. Dickson. Subcellular fate of the int-2 oncoprotein is determined by choice of initiation codon.1990, Nature, v. 343, p. 662-5.

4. Afshari, C. A., P. J. Voj'ta, L. A. Arrnab, P. A. Futreal, Т. B. Willard and J. C. Barrett. Investigation of the role of Gl/S cell cycle mediators in cellular senescence. 1993, Exp Cell Res, v. 209, p. 231-7.

5. Aisen, P. Transferrin, the transferrin receptor, and the uptake of iron by cells.1998, Met Ions Biol Svst. v. 35, p. 585-631.

6. Alessandrini, A., D. S. Chiaur and M. Pagano. Regulation of the cyclin-dependent kinase inhibitor p27 by degradation and phosphorylation. 1997, Leukemia, v. 11, p. 342-5.

7. Alevizopoulos, K., J. Vlach, S. Hennecke and B. Amati. Cyclin E and c-Myc promote cell proliferation in the presence of pl6INK4a and of hypophosphorylatcd retinoblastoma family proteins.1997, Embo J. v. 16, p. 5322-33.

8. Amati, В., S. Dalton, M. W. Brooks, T. D. Littlewood, G. I. Evan and H. Land. Transcriptional activation by the human c-Myc oncoprotein in yeast requires interaction with Max. 1992, Nature, v. 359, p. 423-6.

9. Angel, P., K. Hattori, T. Smeal and M. Karin. The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1.1988, Cell, v. 55, p. 875-85.

10. Antoniades, H. N., D. Stathakos and C. D. Scher. Isolation of a cationic polypeptide from human serum that stimulates proliferation of 3T3 cells. 1975, Proc Natl Acad Sci USA, v. 72, p. 2635-9.

11. Aprelikova, 0., Y. Xiong and E. T. Liu. Both pl6 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by the CDK-activating kinase. 1995, J Biol Chem. v. 270, p. 18195-7.

12. Aronheim, A., D. Engelberg, N. Li, N. al-Alawi, J. Schlessinger and M. Karin. Membrane targeting of the nucleotide exchange factor Sos is sufficient for activating the Ras signaling pathway. 1994, Ce.], v. 78, p. 949-61.

13. Asada, M., T. Yamada, H. Ichijo, D. Delia, K. Miyazono, K. Fukumuro and S. Mizutani. Apoptosis inhibitory activity of cytoplasmic p21(Cipl/WAFl) in monocytic differentiation. 1999. Embo J, v. 18, p. 1223-34.

14. Ashcroft, M. and К. H. Vousden. Regulation of p53 stability. 1999, Oncogene, v. 18, p. 7637-43.

15. Baldin, V., J. Lukas, M. J. Marcote, M. Pagano and G. Draetta. Cyclin D1 is a nuclear protein required for cell cycle progression in G1.1993, Genes Dev, v. 7, p. 812-21.

16. Ballif, B. A. and J. Blenis. Molecular mechanisms mediating mammalian mitogen-activated protein kinase (МАРК) kinase (MEK)-MAPK cell survival signals.2001, Cell Growth Differ, v. 12, p. 397-408.

17. Barone, M. V. and S. A. Courtneidge. Мус but not Fos rescue of PDGF signalling block caused by kinase-inactive Src.1995, Nature, v. 378, p. 509-12.

18. Bartfeld, N. S. and J. H. Law. Isolation and molecular cloning of transferrin from the tobacco hornworm, Manduca sexta. Sequence similarity to the vertebrate transferrins. 1990, J Biol Chem. v. 265, p. 21684-91.

19. Basilico, C. and D. Moscatelli. The FGF family of growth factors and oncogenes. 1992, Adv Cancer Res, v. 59, p. 115-65.

20. Bastians, H., F. M. Townsley and J. V. Ruderman. The cyclin-dependent kinase inhibitor p27(Kipl) induces N-terminal proteolytic cleavage of cyclin A.1998, Proc Natl Acad Sci U S A, v. 95, p. 15374-81.

21. Beijersbergen, R. L., R. M. Kerkhoven, L. Zhu, L. Carlee, P. M. Voorhoeve and R. Bernards. E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with pi 07 in vivo. 1994, Genes Dev. v. 8, p. 2680-90.

22. Beiman, M., B. Z. Shilo and T. Volk. Heartless, a Drosophila FGF receptor homolog, is essential for cell migration and establishment of several mesodermal lineages. 1996, Genes Dev, v. 10, p. 2993-3002.

23. Bergsten, E., M. Uutela, X. Li, K. Pietras, A. Ostman, С. H. Heldin, K. Alitalo and U. Eriksson. PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor.2001, Nat Cell Biol, v. 3, p. 512-6.

24. Betsholtz, C. (1993). The PDGF genes and their regulation. In: Biolosv Platellet-Derived Growth Factor Cytokines. Basel, Karger, S.AG.

25. Bishayee, S., S. Majumdar, J. Khire and M. Das. Ligand-induced dimerization of the platelet-derived growth factor receptor. Monomer-dimer interconversion occurs independent of receptor phosphorylation. 1989, J Biol Chem. v. 264, p. 11699-705.

26. Blackwood, E. M. and R. N. Eisenman. Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Мус.1991. Science, v. 251, p. 1211-7.

27. Blain, S. W., E. Montalvo and J. Massague. Differential interaction of the cyclin-dependent kinase (Cdk) inhibitor p27Kipl with cyclin A-Cdk2 and cyclin D2-Cdk4.1997, J Biol Chem. v. 272, p. 25863-72.

28. Blake, R. A., M. A. Broome, X. Liu, J. Wu, M. Gishizky, L. Sun and S. A. Courtneidge. SU6656, a selective src family kinase inhibitor, used to probe growth factor signaling.2000, Mol Cell Biol, v. 20, p. 9018-27.

29. Bodnar, A. G., M. Ouellette, M. Frolkis, S. E. Holt, C. P. Chiu, G. B. Morin, С. B. Harley, J. W. Shay, S. Lichtsteiner and W. E. Wright. Extension of life-span by introduction of telomerase into normal human cells. 1998, Science, v. 279, p. 349-52.

30. Bonfini, L., C. A. Karlovich, C. Dasgupta and U. Baneijee. The Son of sevenless gene product: a putative activator of Ras.1992, Science, v. 255, p. 603-6.

31. Bonner, J. C., A. Badgett, A. R. Osornio-Vargas, M. Hoffman and A. R. Brody. PDGF-stimulated fibroblast proliferation is enhanced synergistically by receptor-recognized alpha 2-macroglobulin.1990. J Cell Physiol, v. 145, p. 1-8.

32. Bottazzi, M. E., X. Zhu, R. M. Bohmer and R. K. Assoian. Regulation of p21 (cipl) expression by growth factors and the extracellular matrix reveals a role for transient ERK activity in G1 phase.1999, J Cell Biol, v. 146, p. 1255-64.

33. Bowtell, D., P. Fu, M. Simon and P. Senior. Identification of murine homologues of the Drosophila son of sevenless gene: potential activators of ras. 1992, Proc Natl Acad Sci USA, v. 89, p. 6511-5.

34. Brattsand, R. and M. Linden. Cytokine modulation by glucocorticoids: mechanisms and actions in cellular studies. 1996, Aliment Pharmacol Ther. v. 10 Suppl 2, p. 81-90; discussion 91-2.

35. Braun, K., G. Holzl, T. Soucek, C. Geisen, T. Moroy and M. Hengstschlager. Investigation of the cell cycle regulation of cdk3-associated kinase activity and the role of cdk3 in proliferation and transformation. 1998, Oncogene, v. 17, p. 2259-69.

36. Bravo, R., R. Frank, P. A. Blundell and H. Macdonald-Bravo. Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta.1987, Nature, v. 326, p. 515-7.

37. Brehm, A., E. A. Miska, D. J. McCance, J. L. Reid, A. J. Bannister and T. Kouzarides. Retinoblastoma protein recruits histone deacetylase to repress transcription. 1998, Nature, v. 391, p. 597-601.

38. Brickman, M. C. and J. C. Gerhart. Heparitinase inhibition of mesoderm induction and gastrulation in Xenopus laevis embryos.1994, Dev Biol, v. 164, p. 484-501.

39. Brockes, J. P. Amphibian limb regeneration: rebuilding a complex structure. 1997, Science, v. 276, p. 81-7.

40. Broecker, M., J. Hammer and M. Derwahl. Excessive activation of tyrosine kinases leads to inhibition of proliferation in a thyroid carcinoma cell line.1998, Life Sci. v. 63, p. 2373-86.

41. Buchkovich, К., L. A. Duffy and E. Harlow. The retinoblastoma protein is phosphorylated during specific phases of the cell cycle.1989, Cell, v. 58, p. 1097-105.

42. Bugler, В., F. Amalric and H. Prats. Alternative initiation of translation determines cytoplasmic or nuclear localization of basic fibroblast growth factor.1991, Mol Cell Biol, v. 11, p. 573-7.

43. Burgering, В. M. and P. J. Coffer. Protein kinase В (c-Akt) in phosphatidylinositol-3-ОН kinase signal transduction. 1995, Nature, v. 376, p. 599-602.

44. Campochiaro, P. A. Pathogenic mechanisms in proliferative vitreoretinopathy.1997, Arch Ophthalmol, v. 115, p. 237-41.

45. Campochiaro, P. A., R. Sugg, G. Grotendorst and L. M. Hjelmeland. Retinal pigment epithelial cells produce PDGF-like proteins and secrete them into their media. 1989, Exp Eye Res, v. 49, p. 217-27.

46. Castano, E., Y. Kleyner and B. D. Dynlacht. Dual cyclin-binding domains are required for pi07 to function as a kinase inhibitor. 1998, Mol Cell Biol, v. 18, p. 5380-91.

47. Chang, Z. F. and K. Y. Chen. Regulation of ornithine decarboxylase and other cell cycle-dependent genes during senescence of IMR-90 human diploid fibroblasts. 1988, J Biol Chem. v. 263, p. 11431-5.

48. Chen, J., P. K. Jackson, M. W. Kirschner and A. Dutta. Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA.1995, Nature, v. 374, p. 386-8.

49. Chen, T. L., С. M. Cone and D. Feldman. Glucocorticoid modulation of cell proliferation in cultured osteoblast-like bone cells: differences between rat and mouse. 1983, Endocrinology, v. 112, p. 1739-45.

50. Cheng, Т., N. Rodrigues, H. Shen, Y. Yang, D. Dombkowski, M. Sykes and D. T. Scadden. Hematopoietic stem cell quiescence maintained by p21cipl/wafl.2000, Science, v. 287, p. 1804-8.

51. Claesson-Welsh, L. Platelet-derived growth factor receptor signals. 1994, J Biol Chem. v. 269, p. 32023-6.

52. Claesson-Welsh, L., A. Hammacher, B. Westermark, С. H. Heldin and M. Nister. Identification and structural analysis of the A type receptor for platelet-derived growth factor. Similarities with the В type receptor. 1989, J Biol Chem, v. 264, p. 1742-7.

53. Clarke, A. R., E. R. Maandag, M. van Roon, N. M. van der Lugt, M. van der Valk, M. L. Hooper, A. Berns and H. te Riele. Requirement for a functional Rb-1 gene in murine development. 1992, Nature, v. 359, p. 328-30.

54. Cobrinik, D., M. H. Lee, G. Harmon, G. Mulligan, R. T. Bronson, N. Dyson, E. Harlow, D. Beach, R. A. Weinberg and T. Jacks. Shared role of the pRB-related pl30 and pl07 proteins in limb development. 1996. Genes Dev, v. 10, p. 1633-44.

55. Cotsarelis, G., S. Z. Cheng, G. Dong, Т. T. Sun and R. M. Lavker. Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells.1989, Cell, v. 57, p. 201-9.

56. Coulier, F., P. Pontarotti, R. Roubin, H. Hartung, M. Goldfarb and D. Birnbaum. Of worms and men: an evolutionary perspective on the fibroblast growth factor (FGF) and FGF receptor families. 1997, J Mol Evol. v. 44, p. 43-56.

57. Coverley, D., H. Laman and R. A. Laskey. Distinct roles for cyclins E and A during DNA replication complex assembly and activation.2002, Nat Cell Biol, v. 4, p. 523-8.

58. Crews, С. M. and R. L. Erikson. Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byrl gene product. 1992, Proc Natl Acad Sci USA, v. 89, p. 8205-9.

59. Cristofalo, V. J., P. D. Phillips, T. Sorger and G. Gerhard. Alterations in the responsiveness of senescent cells to growth factors. 1989, J Gerontol, v. 44, p. 55-62.

60. Cristofalo, V. J. and В. B. Sharf. Cellular senescence and DNA synthesis. Thymidine incorporation as a measure of population age in human diploid cells. 1973, Exp Cell Res, v. 76, p. 419-27.

61. Cross, D. A., D. R. Alessi, P. Cohen, M. Andjelkovich and B. A. Hemmings. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.1995, Nature, v. 378, p. 785-9.

62. Crossley, P. H. and G. R. Martin. The mouse FgfB gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo. 1995, Development, v. 121, p. 439-51.

63. Daksis, J. I., R. Y. Lu, L. M. Facchini, W. W. Marhin and L. J. Penn. Мус induces cyclin D1 expression in the absence of de novo protein synthesis and links mitogen-stimulated signal transduction to the cell cycle. 1994, Oncogene, v. 9, p. 3635-45.

64. Daniel, Т. О., V. C. Gibbs, D. F. Milfay, M. R. Garovoy and L. T. Williams. Thrombin stimulates c-sis gene expression in microvascular endothelial cells. 1986, J Biol Chem, v. 261, p. 9579-82.

65. Darzynkiewicz, Z., T. Sharpless, L. Staiano-Coico and M. R. Melamed. Subcompartments of the G1 phase of cell cycle detected by flow cytometry. 1980, Proc Natl Acad Sci USA, v. 77, p. 6696-9.

66. De Luca, А., Т. K. MacLachlan, L. Bagella, C. Dean, С. M. Howard, P. P. Claudio, A. Baldi, K. Khalili and A. Giordano. A unique domain of pRb2/pl30 acts as an inhibitor of Cdk2 kinase activity. 1997, J Biol Chem. v. 272, p. 20971-4.

67. DeGregori, J., T. Kowalik and J. R. Nevins. Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and Gl/S-regulatory genes. 1995, Mol Cell Biol, v. 15, p. 4215-24.

68. Dennis, P. A., 0. Saksela, P. Harpel and D. B. Rifkin. Alpha 2-macroglobulin is a binding protein for basic fibroblast growth factor.1989, J Biol Chem. v. 264, p. 7210-6.

69. DePinho, R. A. Transcriptional repression. The cancer-chromatin connection. 1998, Nature, v. 391, p. 533, 535-6.

70. D'Ercole, A. J., D. F. Willson and L. E. Underwood. Changes in the circulating form of serum somatomedin-C during fetal life. 1980, J Clin Endocrinol Metab, v. 51, p. 674-6.

71. Dessev, G., C. Iovcheva-Dessev, J. R. Bischoff, D. Beach and R. Goldman. A complex containing p34cdc2 and cyclin В phosphorylates the nuclear lamin and disassembles nuclei of clam oocytes in vitro.1991, J Cell Biol, v. 112, p. 523-33.

72. DeVore, D. L., H. R. Horvitz and M. J. Stern. An FGF receptor signaling pathway is required for the normal cell migrations of the sex myoblasts in C. elegans hermaphrodites. 1995, Cell, v. 83, p. 611-20.

73. Dickson, C. and P. Acland. Int-2: a member of the fibroblast growth factor family has different subcellular fates depending on the choice of initiation codon.1990, Enzyme, v. 44, p. 225-34.

74. DiCorleto, P. E., С. M. Gajdusek, S. M. Schwartz and R. Ross. Biochemical properties of the endothelium-derived growth factor: comparison to other growth factors. 1983, J Cell Physiol, v. 114, p. 339-45.

75. Diehl, J. A., M. Cheng, M. F. Roussel and C. J. Sherr. Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. 1998, Genes Dev. v. 12, p. 3499511.

76. Doherty, P., P. Smith and F. S. Walsh. Shared cell adhesion molecule (CAM) homology domains point to CAMs signalling via FGF receptors. 1996, Perspect Dev Neurobiol, v. 4, p. 157-68.

77. Doherty, P. and F. S. Walsh. CAM-FGF Receptor Interactions: A Model for Axonal Growth. 1996, Mol Cell Neurosci. v. 8, p. 99-111.

78. Donato, R. S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles.2001. Int J Biochem Cell Biol, v. 33, p. 63768.

79. Donnellan, R. and R. Chetty. Cyclin Dl and human neoplasia. 1998, Mol Pathol, v. 51, p. 1-7.

80. Donohue, P. J., D. K. Hsu, Y. Guo, W. H. Burgess and J. A. Winkles. Fibroblast growth factor-1 induction of delayed-early mRNA expression in NIH 3T3 cells is prolonged by heparin addition. 1997, Exp Cell Res, v. 234, p. 139-46.

81. Dowdy, S. F., P. W. Hinds, K. Louie, S. I. Reed, A. Arnold and R. A. Weinberg. Physical interaction of the retinoblastoma protein with human D cyclins.1993, Cell, v. 73, p. 499-511.

82. Downward, J. Control of ras activation. 1996, Cancer Surv, v. 27, p. 87-100.

83. Drescher-Lincoln, С. K. and J. R. Smith. Inhibition of DNA synthesis in proliferating human diploid fibroblasts by fusion with senescent cytoplasts.1983, Exp Cell Res, v. 144, p. 455-62.

84. Drize, N. J., J. R. Keller and J. L. Chertkov. Local clonal analysis of the hematopoietic system shows that multiple small short-living clones maintain life-long hematopoiesis in reconstituted mice.1996, Blood, v. 88, p. 2927-38.

85. Dulic, V., G. H. Stein, D. F. Far and S. I. Reed. Nuclear accumulation of p21Cipl at the onset of mitosis: a role at the G2/M-phase transition. 1998, Mol Cell Biol, v. 18, p. 546-57.

86. Dunaief, J. L., В. E. Strober, S. Guha, P. A. Khavari, K. Alin, J. Luban, M. Begemann, G. R. Crabtree and S. P. GofT. The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest. 1994, Cell, v. 79, p. 119-30.

87. Dunn, J. F., В. C. Nisula and D. Rodbard. Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma.1981, J Clin Endocrinol Metab. v. 53, p. 58-68.

88. Dunphy, W. G., L. Brizuela, D. Beach and J. Newport. The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis. 1988, Cell, v. 54, p. 423-31.

89. Dunphy, W. G. and A. Kumagai. The cdc25 protein contains an intrinsic phosphatase activity. 1991. Cell, v. 67, p. 189-96.

90. Dynlacht, B. D. Regulation of transcription by proteins that control the cell cycle. 1997, Nature, v. 389, p. 149-52.

91. Egan, S. E., В. W. Giddings, M. W. Brooks, L. Buday, A. M. Sizeland and R. A. Weinberg. Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation. 1993, Nature, v. 363, p. 45-51.

92. Emoto, H., S. Tagashira, M. G. Mattei, M. Yamasaki, G. Hashimoto, T. Katsumata, T. Negoro, M. Nakatsuka, D. Birnbaum, F. Coulier and N. Itoh. Structure and expression of human fibroblast growth factor-10.1997, J Biol Chem. v. 272, p. 23191-4.

93. Ewen, M. E., B. Faha, E. Harlow and D. M. Livingston. Interaction of pi 07 with cyclin A independent of complex formation with viral oncoproteins. 1992, Science, v. 255, p. 85-7.

94. Ewen, M. E., H. K. Sluss, C. J. Sherr, H. Matsushime, J. Kato and D. M. Livingston. Functional interactions of the retinoblastoma protein with mammalian D- type cyclins.1993, Cell, v. 73, p. 487-97.

95. Faha, В., M. E. Ewen, L. H. Tsai, D. M. Livingston and E. Harlow. Interaction between human cyclin A and adenovirus ElA-associated pi07 protein. 1992, Science, v. 255, p. 87-90.

96. Fannon, M. and M. A. Nugent. Basic fibroblast growth factor binds its receptors, is internalized, and stimulates DNA synthesis in Balb/сЗТЗ cells in the absence of heparan sulfate. 1996, J Biol Chem. v. 271, p. 17949-56.

97. Feng, X. H., X. Lin and R. Derynck. Smad2, Smad3 and Smad4 cooperate with Spl to induce pl5(Ink4B) transcription in response to TGF-beta.2000, Embo J. v. 19, p. 5178-93.

98. Femig, D. G. and J. T. Gallagher. Fibroblast growth factors and their receptors: an information network controlling tissue growth, morphogenesis and repair. 1994, Prog Growth Factor Res, v. 5, p. 353-77.

99. Florkiewicz, R. Z., A. Baird and A. M. Gonzalez. Multiple forms of bFGF: differential nuclear and cell surface localization. 1991, Growth Factors, v. 4, p. 265-75.

100. Florkiewicz, R. Z., R. A. Majack, R. D. Buechler and E. Florkiewicz. Quantitative export of FGF-2 occurs through an alternative, energy- dependent, non-ER/Golgi pathway. 1995, J Cell Physiol, v. 162, p. 388-99.

101. Friesel, R. E. and T. Maciag. Molecular mechanisms of angiogenesis: fibroblast growth factor signal transduction. 1995, FasebJ, v. 9, p. 919-25.

102. Froud, S. J. The development, benefits and disadvantages of serum-free media.1999, Dev Biol Stand, v. 99, p. 157-66.

103. Fujiwara, Y. and Т. Kaji. Zinc potentiates the stimulation by basic and acidic fibroblast growth factors on the proliferation of cultured vascular smooth muscle cells. 1997, Res Commun Mol Pathol Pharmacol, v. 97, p. 95-106.

104. Galaktionov, К., X. Chen and D. Beach. Cdc25 cell-cycle phosphatase as a target of c-myc.1996, Nature, v. 382, p. 511-7.

105. Garfinkel, S., J. H. Wessendorf, X. Hu and T. Maciag. The human diploid fibroblast senescence pathway is independent of interleukin-1 alpha mRNA levels and tyrosine phosphorylation of FGFR-1 substrates. 1996, Biochim Biophys Acta, v. 1314, p. 109-19.

106. Gasdaska, J. R., J. H. Law, C. J. Bender and P. Aisen. Cockroach transferrin closely resembles vertebrate transferrins in its metal ion-binding properties: a spectroscopic study. 1996, J Inorg Biochem, v. 64, p. 247-58.

107. Gautier, J., C. Norbury, M. Lohka, P. Nurse and J. Mailer. Purified maturation-promoting factor contains the product of a Xenopus homolog of the fission yeast cell cycle control gene cdc2+.1988, СеП, v. 54, p. 433-9.

108. Gautier, J., M. J. Solomon, R. N. Booher, J. F. Bazan and M. W. Kirschner. cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.1991, Cell, v. 67, p. 197-211.

109. Gemel, J., M. Gorry, G. D. Ehrlich and C. A. MacArthur. Structure and sequence of human FGF8.1996, Genomics, v. 35, p. 253-7.

110. Geng, Y., E. N. Eaton, M. Picon, J. M. Roberts, A. S. Lundberg, A. Gifford, C. Sardet and R. A. Weinberg. Regulation of cyclin E transcription by E2Fs and retinoblastoma protein. 1996, Oncogene, v. 12, p. 1173-80.

111. Geng, Y., Q. Yu, E. Sicinska, M. Das, J. E. Schneider, S. Bhattacharya, W. M. Rideout, R. T. Bronson, H. Gardner and P. Sicinski. Cyclin E ablation in the mouse.2003, Cell, v. 114, p. 431-43.

112. Gianeotti, F. G. A structural view of integrin activation and signaling.2003, Dev Cell, v. 4, p. 149-51.

113. Gille, H., M. Kortenjann, O. Thomae, C. Moomaw, C. Slaughter, M. H. Cobb and P. E. Shaw. ERK phosphorylation potentiates Elk-1-mediated ternary complex formation and transactivation.1995, EmboJ, v. 14, p. 951-62.

114. Ginsberg, D., G. Vairo, T. Chittenden, Z. X. Xiao, G. Xu, K. L. Wydner, J. A. DeCaprio, J. B. Lawrence and D. M. Livingston. E2F-4, a new member of the E2F transcription factor family, interacts with pl07.1994, Genes Dev. v. 8, p. 2665-79.

115. Girard, F., U. Strausfeld, A. Fernandez and N. J. Lamb. Cyclin A is required for the onset of DNA replication in mammalian fibroblasts. 1991, Cell, v. 67, p. 1169-79.

116. Gopalkrishnan, R. V., P. Dolle, M. G. Mattei, N. B. La Thangue and C. Kedinger. Genomic structure and developmental expression of the mouse cell cycle regulatory transcription factor DP 1.1996, Oncogene, v. 13, p. 2671-80.

117. Gospodarowicz, D., A. L. Mescher, K. D. Brown and C. R. Birdwell. The role of fibroblast growth factor and epidermal growth factorin the proliferative response of the corneal and lens epithelium. 1977, Exp Eve Res, v. 25, p. 631 -49.

118. Gottesfeld, J. M., V. J. Wolf, T. Dang, D. J. Forbes and P. Hartl. Mitotic repression of RNA polymerase III transcription in vitro mediated by phosphorylation of a TFIIIB component. 1994, Science, v. 263, p. 81-4.

119. Grandjean, V., J. Smith, P. N. Schofield and A. C. Ferguson-Smith. Increased IGF-II protein affects p57kip2 expression in vivo and in vitro: implications for Beckwith-Wiedemann syndrome.2000, Proc Natl Acad Sci USA, v. 97, p. 5279-84.

120. Grant, M., J. Jerdan and T. J. Merimee. Insulin-like growth factor-I modulates endothelial cell chemotaxis.1987. J Clin Endocrinol Metab. v. 65, p. 370-1.

121. Green, S., M. A. Chiasson and R. G. Shah. Evidence for the presence of an antitumor factor in serum of normal animals. 1979, Cancer Lett, v. 6, p. 235-40.

122. Greenberg, M. E., A. L. Hermanowski and E. B. Ziff. Effect of protein synthesis inhibitors on growth factor activation of c-fos, c-myc, and actin gene transcription. 1986, Mol Cell Biol, v. 6, p. 1050-7.

123. Greenberg, M. E. and E. B. Ziff. Stimulation of 3T3 cells induccs transcription of the c-fos proto-oncogene.1984, Nature, v. 311, p. 433-8.

124. Guo, N., D. V. Faller and C. Vaziri. A novel DNA damage checkpoint involving post-transcriptional regulation of cyclin A expression.2000, J Biol Chem. v. 275, p. 1715-22.

125. Halazonetis, T. D., K. Georgopoulos, M. E. Greenberg and P. Leder. c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities. 1988, Cell, v. 55, p. 917-24.

126. Hammacher, A., M. Nister, B. Westermark and С. H. Heldin. A human glioma cell line secretes three structurally and functionally different dimeric forms of platelet-derived growth factor. 1988, Eur J Biochem. v. 176, p. 179-86.

127. Haniu, M., P. Hsieh, M. F. Rohde and W. C. Kenney. Characterization of disulfide linkages in platelet-derived growth factor AA.1994, Arch Biochem Biophys, v. 310, p. 433-7.

128. Haniu, M., M. F. Rohde and W. C. Kenney. Disulfide bonds in recombinant human platelet-derived growth factor BB dimer: characterization of intermolecular and intramolecular disulfide linkages. 1993, Biochemistry, v. 32, p. 2431-7.

129. Hannon, G. J. and D. Beach. pl5INK4B is a potential effector of TGF-beta-induced cell cycle arrest. 1994, Nature, v. 371, p. 257-61.

130. Hannon, G. J., D. Demetrick and D. Beach. Isolation of the Rb-related pl30 through its interaction with CDK2 and cyclins.1993, Genes Dev. v. 7, p. 2378-91.

131. Hanson, K. D., M. Shichiri, M. R. Follansbee and J. M. Sedivy. Effects of c-myc expression on cell cycle progression. 1994, Mol Cell Biol, v. 14, p. 5748-55.

132. Нага, E., H. Tsurui, A. Shinozaki, S. Nakada and K. Oda. Cooperative effect of antisense-Rb and antisense-p53 oligomers on the extension of life span in human diploid fibroblasts, TIG-1.1991. Biochem Biophys Res Commun, v. 179, p. 528-34.

133. Harlan, J. M., P. J. Thompson, R. R. Ross and D. F. Bowen-Pope. Alpha-thrombin induces release of platelet-derived growth factor-like molecule(s) by cultured human endothelial cells. 1986, J Cell Biol, v. 103, p. 1129-33.

134. Harper, J. W. Cyclin dependent kinase inhibitors. 1997, Cancer Surv, v. 29, p. 91-107.

135. Harper, J. W., G. R. Adami, N. Wei, K. Keyomarsi and S. J. Elledge. The p21 Cdk-interacting protein Cipl is a potent inhibitor of G1 cyclin- dependent kinases. 1993, Cell, v. 75, p. 805-16.

136. Hartung, H., B. Feldman, H. Lovec, F. Coulier, D. Birnbaum and M. Goldfarb. Murine FGF-12 and FGF-13: expression in embryonic nervous system, connective tissue and heart. 1997, Mech Dev. v. 64, p. 31-9.

137. Hattori, Y., M. Yamasaki and N. Itoh. The rat FGF-5 mRNA variant generated by alternative splicing encodes a novel truncated form of FGF-5.1996, Biochim Biophys Acta, v. 1306, p. 31-3.

138. Hayes, Т. E., A. M. Kitchen and В. H. Cochran. Inducible binding of a factor to the c-fos regulatory region.1987, Proc Natl Acad Sci USA, v. 84, p. 1272-6.

139. Hayflick, L. The Limited in Vitro Lifetime of Human Diploid Cell Strains.1965, Exp Cell Res, v. 37, p. 614-36.

140. Heldin, С. H., A. Ernlund, C. Rorsman and L. Ronnstrand. Dimerization of B-type platelet-derived growth factor receptors occurs after ligand binding and is closely associated with receptor kinase activation. 1989, J Biol Chem. v. 264, p. 8905-12.

141. Heldin, С. H. and A. Ostman. Ligand-induced dimerization of growth factor receptors: variations on the theme.1996, Cytokine Growth Factor Rev, v. 7, p. 3-10.

142. Heldin, С. H., A. Wasteson and B. Westermark. Interaction of platelet-derived growth factor with its fibroblast receptor. Demonstration of ligand degradation and receptor modulation. 1982, J Biol Chem. v. 257, p. 4216-21.

143. Heldin, С. H. and B. Westermark. Signal transduction by the receptors for platelet-derived growth factor. 1990, J Cell Sci, v. 96, p. 193-6.

144. Heldin, С. H. and B. Westermark (1996). Role of plateled-derived growth factor in vivo. New York, Plenum Press.

145. Hendrickson, S. L. and C. D. Scher. Platelet-derived growth factor-modulated translatable mRNAs.1983, Mol Cell Biol, v. 3, p. 1478-87.

146. Henglein, В., X. Chenivesse, J. Wang, D. Eick and C. Brechot. Structure and cell cycle-regulated transcription of the human cyclin A gene.1994, Proc Natl Acad Sci USA, v. 91, p. 5490-4.

147. Hengst, L. and S. I. Reed. Translational control of p27Kipl accumulation during the cell cycle. 1996, Science, v. 271, p. 1861-4.

148. Hengstschlager, M., K. Braun, T. Soucek, A. Miloloza and E. Hengstschlager-Ottnad. Cyclin-dependent kinases at the Gl-S transition of the mammalian cell cycle.1999, Mutat Res, v. 436, p. 1-9.

149. Herber, В., M. Truss, M. Beato and R. Muller. Inducible regulatory elements in the human cyclin D1 promoter. 1994, Oncogene, v. 9, p. 1295-304.

150. Herren, B. and M. Pech. Expression of a rat PDGF receptor beta ectodomain generates a low affinity ligand antagonist. 1993, J Recept Res, v. 13, p. 725-38.

151. Hijmans, E. M., P. M. Voorhoeve, R. L. Beijersbergen, L. J. van 4 Veer and R. Bernards. E2F-5, a new E2F family member that interacts with pi30 in vivo. 1995, Mol Cell Biol, v. 15, p. 3082-9.

152. Hinds, P. W., S. Mittnacht, V. Dulic, A. Arnold, S. I. Reed and R. A. Weinberg. Regulation of retinoblastoma protein functions by ectopic expression of human cyclins.1992, Cell, v. 70, p. 993-1006.

153. Hirai, H., M. F. Roussel, J. Y. Kato, R. A. Ashmun and C. J. Sherr. Novel INK4 proteins, pl9 and pl8, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6.1995, Mol Cell Biol, v. 15, p. 2672-81.

154. Hiyama, H., A. Iavarone, J. LaBaer and S. A. Reeves. Regulated ectopic expression of cyclin D1 induces transcriptional activation of the cdk inhibitor p21 gene without altering cell cycle progression. 1997, Oncogene, v. 14, p. 2533-42.

155. Hogg, P. J., K. A. Hotchkiss, В. M. Jimenez, P. Stathakis and C. N. Chesterman. Interaction of platelet-derived growth factor with thrombospondin 1.1997, Biochem J. v. 326 ( Pt3), p. 709-16.

156. Holly, J. M. and J. A. Wass. Insulin-like growth factors; autocrine, paracrine or endocrine? New perspectives of the somatomedin hypothesis in the light of recent developments. 1989, J Endocrinol, v. 122, p. 611-8.

157. Horiuchi, H., T. Inoue, S. Furusawa and H. Matsuda. Cloning and characterization of a chicken platelet-derived growth factor B-chain cDNA.2002, Dev Comp Immunol, v. 26, p. 7383.

158. Horton, L. E. and D. J. Templeton. The cyclin box and C-terminus of cyclins A and E specify CDK activation and substrate specificity. 1997, Oncogene, v. 14, p. 491-8.

159. Horwitz, A., K. Duggan, R. Greggs, C. Decker and C. Buck. The cell substrate attachment (CSAT) antigen has properties of a receptor for laminin and fibronectin.1985, J Cell Biol, v. 101, p. 2134-44.

160. Hu, G. F. Copper stimulates proliferation of human endothelial cells under culture. 1998, J Cell Biochem. v. 69, p. 326-35.

161. Huang, J. S., S. S. Huang and T. F. Deuel. Specific covalent binding of platelet-derived growth factor to human plasma alpha 2-macroglobulin.l984, Proc Natl Acad Sci USA, v. 81, p. 342-6.

162. Huet, X., J. Rech, A. Plet, A. Vie and J. M. Blanchard. Cyclin A expression is under negative transcriptional control during the cell cycle. 1996, Mol Cell Biol, v. 16, p. 3789-98.

163. Hulleman, E. and J. Boonstra. Regulation of G1 phase progression by growth factors and the extracellular matrix.2001. Cell Mol Life Sci. v. 58, p. 80-93.

164. Hurford, R. К., Jr., D. Cobrinik, M. H. Lee and N. Dyson. pRB and pl07/pl30 are required for the regulated expression of different sets of E2F responsive genes.1997, Genes Dev. v. 11, p. 1447-63.

165. Imamura, Т., К. Engleka, X. Zhan, Y. Tokita, R. Forough, D. Roeder, A. Jackson, J. A. Maier, T. Hla and T. Maciag. Recovery of mitogenic activity of a growth factor mutant with a nuclear translocation sequence. 1990, Science, v. 249, p. 1567-70.

166. Itoh, K. and S. Y. Sokol. Heparan sulfate proteoglycans are required for mesoderm formation in Xenopus embryos. 1994, Development, v. 120, p. 2703-11.

167. Jacks, Т., A. Fazeli, E. M. Schmitt, R. T. Bronson, M. A. Goodell and R. A. Weinberg. Effects of an Rb mutation in the mouse. 1992, Nature, v. 359, p. 295-300.

168. Jackson, A., S. Friedman, X. Zhan, K. A. Engleka, R. Forough and T. Maciag. Heat shock induces the release of fibroblast growth factor 1 from NIH 3T3 cells. 1992, Proc Natl Acad Sci USA, v. 89, p. 10691-5.

169. Janknecht, R., W. H. Ernst and A. Nordheim. SAP la is a nuclear target of signaling cascades involving ERKs. 1995, Oncogene, v. 10, p. 1209-16.

170. Jansen-Durr, P., A. Meichle, P. Steiner, M. Pagano, K. Finke, J. Botz, J. Wessbecher, G. Draetta and M. Eilers. Differential modulation of cyclin gene expression by MYC.1993, Proc Natl Acad Sci USA, v. 90, p. 3685-9.

171. Johnston, C. L., H. C. Cox, J. J. Gomm and R. C. Coombes. Fibroblast growth factor receptors (FGFRs) localize in different cellular compartments. A splice variant of FGFR-3 localizes to the nucleus. 1995, J Biol Chem. v. 270, p. 30643-50.

172. Jones, K. L. and J. Addison. Pituitary fibroblast growth factor as a stimulator of growth in cultured rabbit articular chondrocytes. 1975, Endocrinology, v. 97, p. 359-65.

173. Jordan, J. D., E. M. Landau and R. Iyengar. Signaling networks: the origins of ccllular multitasking.2000, Cell, v. 103, p. 193-200.

174. Juliano, R. L. and S. Haskill. Signal transduction from the extracellular matrix.1993, J Cell Biol, v. 120. p. 577-85.

175. Kaftory, A., A. Hershko and M. Fry. Protein turnover in senescent cultured chick embryo fibroblasts. 1978. J Cell Physiol, v. 94, p. 147-60.

176. Kan, M., F. Wang, B. To, J. L. Gabriel and W. L. McKeehan. Divalent cations and heparin/heparan sulfate cooperate to control assembly and activity of the fibroblast growth factor receptor complex.1996, J Biol Chem, v. 271, p. 26143-8.

177. Kaplan, D. R., F. C. Chao, C. D. Stiles, H. N. Antoniades and C. D. Scher. Platelet alpha granules contain a growth factor for fibroblasts. 1979, Blood, v. 53, p. 1043-52.

178. Kasid, A. and M. E. Lippman. Estrogen and oncogene mediated growth regulation of human breast cancer cells. 1987, J Steroid Biochem, v. 27, p. 465-70.

179. Kaufmann, H., R. Marone, M. A. Olayioye, J. E. Bailey and M. Fussenegger. Characterization of an N-terminally truncated cyclin A isoform in mammalian cells.2001, J Biol Chem. v. 276, p. 29987-93.

180. Kazlauskas, A. Receptor tyrosine kinases and their targets. 1994, Curr Opin Genet Dev, v. 4, p. 5-14.

181. Keating, M. T. and L. T. Williams. Processing of the platelet-derived growth factor receptor. Biosynthetic and degradation studies using anti-receptor antibodies. 1987, J Biol Chem. v. 262, p. 7932-7.

182. Kelly, J. L., A. Sanchez, G. S. Brown, C. N. Chesterman and M. J. Sleigh. Accumulation of PDGF В and cell-binding forms of PDGF A in the extracellular matrix. 1993, J Cell Biol, v. 121,p.1153-63.

183. Kiefer, P., G. Peters and C. Dickson. Retention of fibroblast growth factor 3 in the Golgi complex may regulate its export from cells.1993, Mol Cell Biol, v. 13, p. 5781-93.

184. Kim, H. R., S. Upadhyay, G. Li, К. C. Palmer and T. F. Deuel. Platelet-derived growth factor induces apoptosis in growth-arrested murine fibroblasts. 1995, Proc Natl Acad Sci USA, v. 92, p. 9500-4.

185. Kiyono, Т., S. A. Foster, J. I. Koop, J. K. McDougall, D. A. Galloway and A. J. Klingelhutz. Both Rb/pl6INK4a inactivation and telomerase activity are required to immortalize human epithelial cells. 1998, Nature, v. 396, p. 84-8.

186. Knudsen, К. E., A. F. Fribourg, M. W. Strobeck, J. M. Blanchard and E. S. Knudsen. Cyclin A is a functional target of retinoblastoma tumor suppressor protein-mediated cell cycle arrest. 1999, J Biol Chem. v. 274, p. 27632-41.

187. Kohler, N. and A. Lipton. Platelets as a source of fibroblast growth-promoting activity. 1974, Exp Cell Res, v. 87, p. 297-301.

188. Kouhara, H., Y. R. Hadari, T. Spivak-Kroizman, J. Schilling, D. Bar-Sagi, I. Lax and J. Schlessinger. A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway. 1997, Cell, v. 89, p. 693-702.

189. Kourembanas, S., T. Morita, Y. Liu and H. Christou. Mechanisms by which oxygen regulates gene expression and cell-cell interaction in the vasculature. 1997, Kidney Int. v. 51, p. 438-43.

190. Kragh-Hansen, U. Molecular aspects of ligand binding to serum albumin. 1981, Pharmacol Rev, v. 33, p. 17-53.

191. Kretzner, L., E. M. Blackwood and R. N. Eisenman. Мус and Max proteins possess distinct transcriptional activities. 1992, Nature, v. 359, p. 426-9.

192. Krimpenfort, P., К. C. Quon, W. J. Mooi, A. Loonstra and A. Berns. Loss of pl6Ink4a confers susceptibility to metastatic melanoma in mice.2001, Nature, v. 413, p. 83-6.

193. Krude, Т., M. Jackman, J. Pines and R. A. Laskey. Cyclin/Cdk-dependent initiation of DNA replication in a human cell-free system. 1997, Cell, v. 88, p. 109-19.

194. Kunimoto, В. T. Growth factors in wound healing: the next great innovation? 1999, Ostomy Wound Manage, v. 45, p. 56-64; quiz 65-6.

195. Kurtz, A., W. Hartl, W. Jelkmann, J. Zapf and C. Bauer. Activity in fetal bovine serum that stimulates erythroid colony formation in fetal mouse livers is insulinlike growth factor 1.1985, J Clin Invest, v. 76, p. 1643-8.

196. La Thangue, N. B. DRTF1/E2F: an expanding family of heterodimeric transcription factors implicated in cell-cycle control.1994, Trends Biochem Sci. v. 19, p. 108-14.

197. Landriscina, M., R. Soldi, C. Bagala, I. Micucci, S. Bellum, F. Tarantini, I. Prudovsky and T. Maciag. S100A13 participates in the release of fibroblast growth factor 1 in response to heat shock in vitro.2001. J Biol Chem. v. 276, p. 22544-52.

198. LaRochelle, W. J., M. May-Siroff, К. C. Robbins and S. A. Aaronson. A novel mechanism regulating growth factor association with the cell surface: identification of a PDGF retention domain.1991. Genes Dev. v. 5, p. 1191-9.

199. Larsen, С. J. pl6INK4a: a gene with a dual capacity to encode unrelated proteins that inhibit cell cycle progression. 1996, Oncogene, v. 12, p. 2041-4.

200. Larsson, O., A. Zetterberg and W. Engstrom. Cell-cycle-specific induction of quiescence achieved by limited inhibition of protein synthesis: counteractive effect of addition of purified growth factors. 1985, J Cell Sci. v. 73, p. 375-87.

201. Larsson, O., A. Zetterberg and W. Engstrom. Consequences of parental exposure to serum-free medium for progeny cell division. 1985, J Cell Sci. v. 75, p. 259-68.

202. Lauper, N., A. R. Beck, S. Cariou, L. Richman, K. Hofmann, W. Reith, J. M. Slingerland and B. Amati. Cyclin E2: a novel CDK2 partner in the late G1 and S phases of the mammalian cell cycle. 1998, Oncogene, v. 17, p. 2637-43.

203. LaVallee, Т. M., F. Tarantini, S. Gamble, C. Mouta Carreira, A. Jackson and T. Maciag. Synaptotagmin-1 is required for fibroblast growth factor-1 release.1998, J Biol Chem, v. 273, p. 22217-23.

204. Lawlor, M. A., X. Feng, D. R. Everding, K. Sieger, С. E. Stewart and P. Rotwein. Dual control of muscle cell survival by distinct growth factor-regulated signaling pathways.2000, Mol Cell Biol, v. 20, p. 3256-65.

205. Lee, E. Y., C. Y. Chang, N. Hu, Y. C. Wang, С. C. Lai, K. Herrup, W. H. Lee and A. Bradley. Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis. 1992, Nature, v. 359, p. 288-94.

206. Lee, M. H., В. O. Williams, G. Mulligan, S. Mukai, R. T. Bronson, N. Dyson, E. Harlow and T. Jacks. Targeted disruption of pi07: functional overlap between pi07 and Rb.1996, Genes Dev. v. 10, p. 1621-32.

207. Lee, Т. C., L. Li, L. Philipson and E. B. Ziff. Мус represses transcription of the growth arrest gene gas 1.1997, Proc Natl Acad Sci USA, v. 94, p. 12886-91.

208. Lees, E., В. Faha, V. Dulic, S. I. Reed and E. Harlow. Cyclin E/cdk2 and cyclin A/cdk2 kinases associate with pi07 and E2F in a temporally distinct manner. 1992, Genes Dev, v. 6, p. 1874-85.

209. Leevers, S. J., H. F. Paterson and C. J. Marshall. Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane. 1994, Nature, v. 369, p. 411-4.

210. Leone, G., J. DeGregori, Z. Yan, L. Jakoi, S. Ishida, R. S. Williams and J. R. Nevins. E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. 1998, Genes Dev, v. 12, p. 2120-30.

211. Levin, D. S., W. Bai, N. Yao, M. O'Donnell and A. E. Tomkinson. An interaction between DNA ligase I and proliferating cell nuclear antigen: implications for Okazaki fragment synthesis and joining. 1997, Proc Natl Acad Sci USA, v. 94, p. 12863-8.

212. Li, N., A. Batzer, R. Daly, V. Yajnik, E. Skolnik, P. Chardin, D. Bar-Sagi, B. Margolis and J. Schlessinger. Guanine-nucleotide-releasing factor hSosl binds to Grb2 and links receptor tyrosine kinases to Ras signalling. 1993, Nature, v. 363, p. 85-8.

213. Li, R., S. Waga, G. J. Hannon, D. Beach and B. Stillman. Differential effects by the p21 CDK inhibitor on PCNA-dependent DNA replication and repair.1994, Nature, v. 371, p. 534-7.

214. Li, S. and G. D. Shipley. Expression of multiple species of basic fibroblast growth factor mRNA and protein in normal and tumor-derived mammary epithelial cells in culture. 1991, Cell Growth Differ, v. 2, p. 195-202.

215. Li, Y., C. Graham, S. Lacy, A. M. Duncan and P. Whyte. The adenovirus ElA-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E.1993, Genes Dev, v. 7, p. 2366-77.

216. Limat, A. and L. E. French. Therapy with growth factors. 1999, Curr Probl Dermatol, v. 27, p. 49-56.

217. Lorca, Т., J. C. Labbe, A. Devault, D. Fesquet, J. P. Capony, J. C. Cavadore, F. Le Bouffant and M. Doree. Dephosphorylation of cdc2 on threonine 161 is required for cdc2 kinase inactivation and normal anaphase. 1992, EmboJ, v. 11, p. 2381-90.

218. Lorimer, I. A. Mutant epidermal growth factor receptors as targets for cancer therapy.2002, Curr Cancer Drug Targets, v. 2, p. 91-102.

219. Ludlow, J. W., C. L. Glendening, D. M. Livingston and J. A. DeCarprio. Specific enzymatic dephosphorylation of the retinoblastoma protein.1993, Mol Cell Biol, v. 13, p. 36772.

220. Lukas, J., T. Herzinger, K. Hansen, M. C. Moroni, D. Resnitzky, K. Helin, S. I. Reed and J. Bartek. Cyclin E-induced S phase without activation of the pRb/E2F pathway.1997, Genes Dev, v. 11, p. 1479-92.

221. Lumpkin, С. K., Jr., J. K. McClung, О. M. Pereira-Smith and J. R. Smith. Existence of high abundance antiproliferative mRNA's in senescent human diploid fibroblasts. 1986, Science, v. 232, p. 393-5.

222. Lundberg, A. S., W. C. Hahn, P. Gupta and R. A. Weinberg. Genes involved in senescence and immortalization.2000, Curr Opin Cell Biol, v. 12, p. 705-9.

223. Lundgren, K., N. Walworth, R. Booher, M. Dembski, M. Kirschner and D. Beach, mikl and weel cooperate in the inhibitory tyrosine phosphorylation of cdc2.1991, Cell, v. 64, p. 1111-22.

224. Luo, R. X., A. A. Postigo and D. C. Dean. Rb interacts with histone deacetylase to repress transcription. 1998, Ccl., v. 92, p. 463-73.

225. Macdonald, S. Gi, С. M. Crews, L. Wu, J. Driller, R. Clark, R. L. Erikson and F. McCormick. Reconstitution of the Raf-l-MEK-ERK signal transduction pathway in vitro. 1993, Mol Cell Biol, v. 13, p. 6615-20.

226. Maciag, Т., J. Cerundolo, S. Ilsley, P. R. Kelley and R. Forand. An endothelial cell growth factor from bovine hypothalamus: identification and partial characterization. 1979, Proc Natl Acad Sci USA, v. 76, p. 5674-8.

227. Maciag, Т., G. A. Hoover, M. B. Stemerman and R. Weinstein. Serial propagation of human endothelial cells in vitro.1981, J Cell Biol, v. 91, p. 420-6.

228. Maciag, Т., Т. Mehlman, R. Friesel and A. B. Schreiber. Heparin binds endothelial cell growth factor, the principal endothelial cell mitogen in bovine brain. 1984, Science, v. 225, p. 932-5.

229. Madine, M. A., M. Swietlik, C. Pelizon, P. Romanowski, A. D. Mills and R. A. Laskey. The roles of the MCM, ORC, and Cdc6 proteins in determining the replication competence of chromatin in quiescent cells.2000, J Struct Biol, v. 129, p. 198-210.

230. Maher, P. A. Identification and characterization of a novel, intracellular isoform of fibroblast growth factor receptor-1 (FGFR-1). 1996, J Cell Physiol, v. 169, p. 380-90.

231. Maier, J. A., P. Voulalas, D. Roeder and T. Maciag. Extension of the life-span of human endothelial cells by an interleukin-1 alpha antisense oligomer. 1990, Science, v. 249, p. 1570-4.

232. Makela, T. P., J. P. Tassan, E. A. Nigg, S. Frutiger, G. J. Hughes and R. A. Weinberg. A cyclin associated with the CDK-activating kinase M015.1994, Nature, v. 371, p. 254-7.

233. Masui, Y. and C. L. Markert. Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes.1971, J Exp Zool, v. 177, p. 129-45.

234. Masuoka, J. and P. Saltman. Zinc(II) and copper(II) binding to serum albumin. A comparative study of dog, bovine, and human albumin. 1994, J Biol Chem. v. 269, p. 25557-61.

235. Mather, J. P. Making informed choices: medium, serum, and serum-free medium. How to choose the appropriate medium and culture system for the model you wish to create. 1998, Methods Cell Biol, v. 57, p. 19-30.

236. Matsui, Т., M. Heidaran, T. Miki, N. Popescu, W. La Rochelle, M. Kraus, J. Pierce and S. Aaronson. Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes. 1989, Science, v. 243, p. 800-4.

237. Matsumura, Т., Z. Zerrudo and L. Hayflick. Senescent human diploid cells in culture: survival, DNA synthesis and morphology. 1979, J Gerontol, v. 34, p. 328-34.

238. Matsuoka, J. and G. R. Grotendorst. Two peptides related to platelet-derived growth factor are present in human wound fluid. 1989, Proc Natl Acad Sci USA, v. 86, p. 4416-20.

239. Matsushime, H., D. E. Quelle, S. A. Shurtleff, M. Shibuya, C. J. Sherr and J. Y. Kato. D-type cyclin-dependent kinase activity in mammalian cells. 1994, Mol Cell Biol, v. 14, p. 206676.

240. Matsushime, H., M. F. Roussel, R. A. Ashmun and C. J. Sherr. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle.1991, Cell, v. 65, p. 701-13.

241. Maurer, H. R. (1986). Towards chemically-defined, serum-free media for mammalian cells culture. IRS Press Limited.

242. McAuslan, B. R. and W. Reilly. Selenium-induced cell migration and proliferation: relevance to angiogenesis and microangiopathy.!986, Microvasc Res, v. 32, p. 112-20.

243. McCoon, P. E., R. C. Angerer and L. M. Angerer. SpFGFR, a new member of the fibroblast growth factor receptor family, is developmentally regulated during early sea urchin development. 1996, J Biol Chem. v. 271, p. 20119-25.

244. McDonnell, T. J. and J. O. Oberpriller. The atrial proliferative response following partial ventricular amputation in the heart of the adult newt. A light and electron microscopic autoradiographic study.1983, Tissue Cell, v. 15, p. 351-63.

245. McGowan, С. H. and P. Russell. Human Weel kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyrl5.1993, Embo J. v. 12, p. 75-85.

246. Mendez, J. and B. Stillman. Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis.2000, Mol Cell Biol, v. 20, p. 8602-12.

247. Mercola, M., D. A. Melton and C. D. Stiles. Platelet-derived growth factor A chain is maternally encoded in Xenopus embryos.1988, Science, v. 241, p. 1223-5.

248. Mercola, M., C. Y. Wang, J. Kelly, C. Brownlee, L. Jackson-Grusby, C. Stiles and D. Bowen-Pope. Selective expression of PDGF A and its receptor during early mouse embrvogenesis.1990. Dev Biol, v. 138, p. 114-22.

249. Mihara, К., X. R. Cao, A. Yen, S. Chandler, B. Driscoll, A. L. Murphree, A. T'Ang and Y. K. Fung. Cell cycle-dependent regulation of phosphorylation of the human retinoblastoma gene product. 1989, Science, v. 246, p. 1300-3.

250. Millar, J. В., J. Blevitt, L. Gerace, K. Sadhu, C. Featherstone and P. Russell. p55CDC25 is a nuclear protein required for the initiation of mitosis in human cells. 1991, Proc Natl Acad Sci USA, v. 88, p. 10500-4.

251. Minshull, J., R. Golsteyn, C. S. Hill and T. Hunt. The A- and B-type cyclin associated cdc2 kinases in Xenopus turn on and off at different times in the cell cycle.1990, Embo J, v. 9, p. 2865-75.

252. Mohammadi, M., C. A. Dionne, W. Li, N. Li, T. Spivak, A. M. Honegger, M. Jaye and J. Schlessinger. Point mutation in FGF receptor eliminates phosphatidylinositol hydrolysis without affecting mitogenesis.1992, Nature, v. 358, p. 681-4.

253. Molloy, Т., Y. Wang and G. Murrell. The roles of growth factors in tendon and ligament healing.2003, Sports Med, v. 33, p. 381-94.

254. Moodie, S. А., В. M. Willumsen, M. J. Weber and A. Wolfman. Complexes of Ras.GTP with Raf-1 and mitogen-activated protein kinase kinase. 1993, Science, v. 260, p. 1658-61.

255. Morgan, D. O. The dynamics of cyclin dependent kinase structure. 1996, Curr Opin Cell Biol, v. 8, p. 767-72.

256. Morgan, D. О., R. P. Fisher, F. H. Espinoza, A. Farrell, J. Nourse, H. Chamberlin and P. Jin. Control of eukaryotic cell cycle progression by phosphorylation of cyclin-dependent kinases. 1998, Cancer J Sci Am. v. 4 Suppl 1, p. S77-83.

257. Morisaki, H., A. Fujimoto, A. Ando, Y. Nagata, K. Ikeda and M. Nakanishi. Cell cycle-dependent phosphorylation of p27 cyclin-dependent kinase (Cdk) inhibitor by cyclin E/Cdk2.1997, Biochem Biophys Res Commun. v. 240, p. 386-90.

258. Morrison-Graham, K., G. C. Schatteman, T. Bork, D. F. Bowen-Pope and J. A. Weston. A PDGF receptor mutation in the mouse (Patch) perturbs the development of a non-neuronal subset of neural crest-derived cells. 1992, Development, v. 115, p. 133-42.

259. Morse, L., D. Chen, D. Franklin, Y. Xiong and S. Chen-Kiang. Induction of cell cycle arrest and В cell terminal differentiation by CDK inhibitor pl8(INK4c) and IL-6.1997, Immunity, v. 6, p. 47-56.

260. Mueller, P. R., T. R. Coleman, A. Kumagai and W. G. Dunphy. Mytl: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15.1995, Science, v. 270, p. 86-90.

261. Muller, R., R. Bravo, J. Burckhardt and T. Curran. Induction of c-fos gene and protein by growth factors precedes activation of c-myc.1984, Nature, v. 312, p. 716-20.

262. Munoz, R., O. Klingenberg, A. Wiedlocha, A. Rapak, P. O. Falnes and S. Olsnes. Effect of mutation of cytoplasmic receptor domain and of genistein on transport of acidic fibroblast growth factor into cells. 1997, Oncogene, v. 15, p. 525-36.

263. Murai, Т., Y. Nakagawa, H. Maeda and K. Terada. Altered regulation of cell cycle machinery involved in interleukin-1-induced G(l) and G(2) phase growth arrest of A375S2 human melanoma cells.2001, J Biol Chem, v. 276, p. 6797-806.

264. Murray, A. W., M. J. Solomon and M. W. Kirschner. The role of cyclin synthesis and degradation in the control of maturation promoting factor activity. 1989, Nature, v. 339, p. 2806.

265. Murzin, A. G., A. M. Lesk and C. Chothia. beta-Trefoil fold. Patterns of structure and sequence in the Kunitz inhibitors interleukins-1 beta and 1 alpha and fibroblast growth factors. 1992, J Mol Biol, v. 223, p. 531-43.

266. Nagata, К., M. J. Humphries, К. Olden and К. M. Yamada. Collagen can modulate cell interactions with fibronectin.1985, J Cell Biol, v. 101, p. 386-94.

267. Nakabeppu, Y., K. Ryder and D. Nathans. DNA binding activities of three murine Jun proteins: stimulation by Fos.1988, Cell, v. 55, p. 907-15.

268. Nakanishi, M., R. S. Robetorye, G. R. Adami, О. M. Pereira-Smith and J. R. Smith. Identification of the active region of the DNA synthesis inhibitory gene p21Sdil/CIPl/WAF1.1995, Embo J. v. 14, p. 555-63.

269. Nevins, J. R., G. Leone, J. DeGregori and L. Jakoi. Role of the Rb/E2F pathway in cell growth control.1997, J Cell Physiol, v. 173, p. 233-6.

270. Nilsson, J., M. Sjolund, L. Palmberg, J. Thyberg and С. H. Heldin. Arterial smooth muscle cells in primary culture produce a platelet-derived growth factor-like protein.1985, Proc Natl Acad Sci USA, v. 82, p. 4418-22.

271. Nissen, N. N., P. J. Polverini, R. L. Gamelli and L. A. DiPietro. Basic fibroblast growth factor mediates angiogenic activity in early surgical wounds. 1996, Surgery, v. 119, p. 457-65.

272. Noda, A., Y. Ning, S. F. Venable, О. M. Pereira-Smith and J. R. Smith. Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. 1994, Exp Cell Res, v. 211, p. 90-8.

273. Norwood, Т. H., W. R. Pendergrass, C. A. Sprague and G. M. Martin. Dominance of the senescent phenotype in heterokaryons between replicative and post-replicative human fibroblast-like cells. 1974, Proc Natl Acad Sci USA, v. 71, p. 2231-5.

274. Obaya, A. J. and J. M. Sedivy. Regulation of cyclin-Cdk activity in mammalian cells.2002, Cell Mol Life Sci. v. 59, p. 126-42.

275. O'Connor-McCourt, M. D. and L. M. Wakefield. Latent transforming growth factor-beta in serum. A specific complex with alpha 2-macroglobulin.l987, J Biol Chem, v. 262, p. 14090-9.

276. Oda, S., J. Nishida, Y. Nakabeppu and M. Sekiguchi. Stabilization of cyclin E and cdk2 mRNAs at Gl/S transition in Rat-IA cells emerging from the GO state.1995, Oncogene, v. 10, p. 1343-51.

277. Ogawa, M. Differentiation and proliferation of hematopoietic stem cells.1993, Blood, v. 81, p. 2844-53.

278. Ogryzko, V. V., P. Wong and В. H. Howard. WAF1 retards S-phase progression primarily by inhibition of cyclin-dependent kinases. 1997, Mol Cell Biol, v. 17, p. 4877-82.

279. Ohtsubo, M., A. M. Theodoras, J. Schumacher, J. M. Roberts and M. Pagano. Human cyclin E, a nuclear protein essential for the Gl-to-S phase transition. 1995, Mol Cell Biol, v. 15, p. 2612-24.

280. Oikawa, T. and T. Yamada. Molecular biology of the Ets family of transcription factors.2003, Gene, v. 303, p. 11-34.

281. Omitz, D. M. and N. Itoh. Fibroblast growth factors.2001, Genome Biol, v. 2, p. REVIEWS3005.

282. Orr-Urtreger, A. and P. Lonai. Platelet-derived growth factor-A and its receptor are expressed in separate, but adjacent cell layers of the mouse embryo. 1992, Development, v. 115, p. 1045-58.

283. O'Shea, E. K., R. Rutkowski, W. F. Stafford, 3rd and P. S. Kim. Preferential heterodimer formation by isolated leucine zippers from fos and jun. 1989, Science, v. 245, p. 646-8.

284. Pagano, M., R. Pepperkok, F. Verde, W. Ansorge and G. Draetta. Cyclin A is required at two points in the human ccll cycle. 1992, Embo J. v. 11, p. 961-71.

285. Pagano, M., A. M. Theodoras, S. W. Tam and G. F. Draetta. Cyclin D1-mediated inhibition of repair and replicative DNA synthesis in human fibroblasts. 1994, Genes Dev. v. 8, p. 1627-39.

286. Pardee, A. B. A restriction point for control of normal animal cell proliferation. 1974, Proc Natl Acad Sci USA, v. 71, p. 1286-90.

287. Parker, L. L. and H. Piwnica-Worms. Inactivation of the p34cdc2-cyclin В complex by the human WEE1 tyrosine kinase. 1992, Science, v. 257, p. 1955-7.

288. Patry, V., В. Bugler, A. Maret, M. Potier and H. Prats. Endogenous basic fibroblast growth factor isoforms involved in different intracellular protein complexes. 1997, Biochem J, v. 326, p. 259-64.

289. Patstone, G. and P. Maher. Copper and calcium binding motifs in the extracellular domains of fibroblast growth factor receptors. 1996, J Biol Chem, v. 271, p. 3343-6.

290. Paulsson, Y., A. Hammacher, С. H. Heldin and B. Westermark. Possible positive autocrine feedback in the prereplicative phase of human fibroblasts. 1987, Nature, v. 328, p. 715-7.

291. Pawson, T. and Т. M. Saxton. Signaling networks—do all roads lead to the same genes? 1999, Cell, v. 97, p. 675-8.

292. Payne, W. G., D. E. Ochs, D. D. Meltzer, D. P. Hill, R. J. Mannari, L. E. Robson and M. C. Robson. Long-term outcome study of growth factor-treated pressure ulcers.2001, Am J Surg, v. 181, p. 81-6.

293. Pearson, J., P. M. Keane and W. H. Walker. Binding of Cortisol to human albumin. 1967, Nature, v. 216, p. 1334-5.

294. Репа, A., C. D. Reddy, S. Wu, N. J. Hickok, E. P. Reddy, G. Yumet, D. R. Soprano and K. J. Soprano. Regulation of human ornithine decarboxylase expression by the c-Myc.Max protein complex.1993, J Biol Chem. v. 268, p. 27277-85.

295. Pepperkok, R., M. Zanetti, R. King, D. Delia, W. Ansorge, L. Philipson and C. Schneider. Automatic microinjection system facilitates detection of growth inhibitory mRNA.1988, Proc Natl Acad Sci USA, v. 85, p. 6748-52.

296. Peters, K. G., J. Marie, E. Wilson, H. E. Ives, J. Escobedo, M. Del Rosario, D. Mirda and L. T. Williams. Point mutation of an FGF receptor abolishes phosphatidylinositol turnover and Ca2+ flux but not mitogenesis.1992, Nature, v. 358, p. 678-81.

297. Peters, Т., Jr. Serum albumin.1985, Adv Protein Chem. v. 37, p. 161-245.

298. Phelan, M. L., S. Sif, G. J. Narlikar and R. E. Kingston. Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits.1999, Mol Cell, v. 3, p. 247-53.

299. Piaggio, G., A. Farina, D. Perrotti, I. Manni, P. Fuschi, A. Sacchi and C. Gaetano. Structure and growth-dependent regulation of the human cyclin B1 promoter. 1995, Exp Cell Res, v. 216, p. 396-402.

300. Pines, J. and T. Hunter. Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2.1989, Cell, v. 58, p. 833-46.

301. Pines, J. and T. Hunter. Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport. 1991. J Cell Biol, v. 115, p. 1-17.

302. Pohjanpelto, P. Stimulation of DNA synthesis in human fibroblasts by thrombin. 1978, J Cell Physiol, v. 95, p. 189-94.

303. Powell, P. P. and M. Klagsbrun. Three forms of rat basic fibroblast growth factor are made from a single mRNA and localize to the nucleus.1991, J Cell Physiol, v. 148, p. 202-10.

304. Powers, C. J., S. W. McLeskey and A. Wellstein. Fibroblast growth factors, their receptors and signaling.2000, Endocr Relat Cancer, v. 7, p. 165-97.

305. Prelich, G., M. Kostura, D. R. Marshak, M. B. Mathews and B. Stillman. The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro. 1987, Nature, v. 326, p. 471-5.

306. Prudovsky, I., N. Savion, X. Zhan, R. Friesel, J. Xu, J. Hou, W. L. McKeehan and T. Maciag. Intact and functional fibroblast growth factor (FGF) receptor-1 trafficks near the nucleus in response to FGF-1.1994, J Biol Chem. v. 269, p. 31720-4.

307. Pytela, R., M. D. Pierschbacher and E. Ruoslahti. Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor. 1985, Cell, v. 40, p. 191-8.

308. Rahmsdorf, H. J., A. Schonthal, P. Angel, M. Litfin, U. Ruther and P. Herrlich. Posttranscriptional regulation of c-fos mRNA expression. 1987, Nucleic Acids Res, v. 15, p. 1643-59.

309. Raines, E. W., D. F. Bowen-Pope and R. Ross (1990). Plateled-derived growth factor. In: Sporn. M.B.

310. Roberts. A.B. (Eds.): Handbook o f Experimental Pharmacology. Peptide Growth Factors and Their Receptors Vol.95, part 1.

311. Raines, E. W., S. K. Dower and R. Ross. Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA.1989, Science, v. 243, p. 393-6.

312. Rao, V. N. and E. S. Reddy. elk-1 proteins interact with MAP kinases. 1994, Oncogene, v. 9, p. 1855-60.

313. Ray, S. К., X. Q. Yang and I. M. Chiu. Transcriptional activation of fibroblast growth factor l.B promoter is mediated through an 18-base pair cis-acting element. 1997, J Biol Chem. v. 272, p. 7546-55.

314. Reed, S. I. Cyclin E: in mid-cycle. 1996, Biochim Biophys Acta, v. 1287, p. 151-3.

315. Reed, S. I. Control of the Gl/S transition. 1997, Cancer Surv, v. 29, p. 7-23.

316. Reichman-Fried, M. and B. Z. Shilo. Breathless, a Drosophila FGF receptor homolog, is required for the onset of tracheal cell migration and tracheole formation. 1995, Mech Dev. v. 52, p. 265-73.

317. Renaud, F., I. El Yazidi, Y. Boilly-Marer, Y. Courtois and M. Laurent. Expression and regulation by serum of multiple FGF1 mRNA in normal transformed, and malignant human mammary epithelial cells. 1996, Biochem Biophys Res Commun. v. 219, p. 679-85.

318. Renaud, F., L. Oliver, S. Desset, J. Tassin, N. Romquin, Y. Courtois and M. Laurent. Up-regulation of aFGF expression in quiescent cells is related to cell survival. 1994, J Cell Physiol, v. 158, p. 435-43.

319. Resnitzky, D. Ectopic expression of cyclin D1 but not cyclin E induces anchorage-independent cell cycle progression. 1997, Mol Cell Biol, v. 17, p. 5640-7.

320. Resnitzky, D., M. Gossen, H. Bujard and S. I. Reed. Acceleration of the Gl/S phase transition by expression of cyclins D1 and E with an inducible system.1994, Mol Cell Biol, v. 14, p. 1669-79.

321. Resnitzky, D. and S. I. Reed. Different roles for cyclins D1 and E in regulation of the Gl-to-S transition. 1995. Mol Cell Biol, v. 15, p. 3463-9.

322. Reuterdahl, С., C. Sundberg, K. Rubin, K. Funa and B. Gerdin. Tissue localization of beta receptors for platelet-derived growth factor and platelet-derived growth factor В chain during wound repair in humans.1993, J Clin Invest, v. 91, p. 2065-75.

323. Riabowol, K., J. Schiff and M. Z. Gilman. Transcription factor AP-1 activity is required for initiation of DNA synthesis and is lost during cellular aging. 1992, Proc Natl Acad Sci U S A, v. 89, p. 157-61.

324. Roghani, M., A. Mansukhani, P. DeU'Era, P. Bellosta, C. Basilico, D. B. Rifkin and D. Moscatelli. Heparin increases the affinity of basic fibroblast growth factor for its receptor but is not required for binding. 1994, J Biol Chem. v. 269, p. 3976-84.

325. Roovers, К. and R. К. Assoian. Integrating the MAP kinase signal into the G1 phase cell cycle machinery.2000, Bioessavs. v. 22, p. 818-26.

326. Rosenberg, A. R., F. Zindy, F. Le Deist, H. Mouly, P. Metezeau, C. Brechot and E. Lamas. Overexpression of human cyclin A advances entry into S phase. 1995, Oncogene, v. 10, p. 15019.

327. Rosengart, Т. K., W. V. Johnson, R. Friesel, R. Clark and T. Maciag. Heparin protects heparin-binding growth factor-I from proteolytic inactivation in vitro. 1988, Biochem Biophys Res Commun. v. 152, p. 432-40.

328. Ross, R., J. Glomset, B. Kariya and L. Harker. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro.1974, Proc Natl Acad Sci U S A. v. 71, p. 1207-10.

329. Ross, R., C. Nist, B. Kariya, M. J. Rivest, E. Raines and J. Callis. Physiological quiescence in plasma-derived serum: influence of platelet-derived growth factor on cell growth in culture.1978, J Cell Physiol, v. 97, p. 497-508.

330. Roth, M., M. Nauck, M. Tamm, A. P. Perruchoud, R. Ziesche and L. H. Block. Intracellular interleukin 6 mediates platelet-derived growth factor-induced proliferation of nontransformed cells. 1995, Proc Natl Acad Sci USA, v. 92, p. 1312-6.

331. Roussel, M. F., J. N. Davis, J. L. Cleveland, J. Ghysdael and S. W. Hiebert. Dual control of myc expression through a single DNA binding site targeted by ets family proteins and E2F-1.1994, Oncogene, v. 9, p. 405-15.

332. Rufer, N., M. Migliaccio, J. Antonchuk, R. K. Humphries, E. Roosnek and P. M. Lansdorp. Transfer of the human telomerase reverse transcriptase (TERT) gene into T lymphocytes results in extension of replicative potential.2001. Blood, v. 98, p. 597-603.

333. Sahni, M., D. C. Ambrosetti, A. Mansukhani, R. Gertner, D. Levy and C. Basilico. FGF signaling inhibits chondrocyte proliferation and regulates bone development through the STAT-1 pathway. 1999. Genes Dev. v. 13, p. 1361-6.

334. Sato, N., I. M. Sanjuan, M. Hekc, M. Uchida, F. Naef and A. H. Brivanlou. Molecular signature of human embryonic stem cells and its comparison with the mouse.2003, Dev Biol, v. 260, p. 404-13.

335. Schatteman, G. С., К. Morrison-Graham, A. van Koppen, J. A. Weston and D. F. Bowen-Pope. Regulation and role of PDGF receptor alpha-subunit expression during embryogenesis.1992, Development, v. 115, p. 123-31.

336. Scher, C. D., D. Stathakos and H. N. Antoniades. Dissociation of cell division stimulating capacity for Balb-c-3T3 from the insulin-like activity in human serum. 1974, Nature, v. 247, p. 279-81.

337. Schiavo, G., S. L. Osborne and J. G. Sgouros. Synaptotagmins: more isoforms than functions? 1998, Biochem Biophys Res Commun, v. 248, p. 1-8.

338. Schneider, C., R. M. King and L. Philipson. Genes specifically expressed at growth arrest of mammalian cells.1988, Cell, v. 54, p. 787-93.

339. Schulze-Lohoff, E., K. Brand, H. Fees, R. Netzker and R. B. Sterzel. Role of ornithine decarboxylase for proliferation of mesangial cells in culture. 1991, Kidney Int, v. 40, p. 684-90.

340. Sears, R., G. Leone, J. DeGregori and J. R. Nevins. Ras enhances Мус protein stability. 1999, Mol Cell, v. 3, p. 169-79.

341. Sears, R., K. Ohtani and J. R. Nevins. Identification of positively and negatively acting elements regulating expression of the E2F2 gene in response to cell growth signals. 1997, Mol Cell Biol, v. 17, p. 5227-35.

342. Seifert, R. А., С. E. Hart, P. E. Phillips, J. W. Forstrom, R. Ross, M. J. Murray and D. F. Bowen-Pope. Two different subunits associate to create isoform-specific platelet-derived growth factor receptors. 1989, J Biol Chem. v. 264, p. 8771-8.

343. Seifert, R. A., S. M. Schwartz and D. F. Bowen-Pope. Developmentally regulated production of platelet-derived growth factor-like molecules. 1984, Nature, v. 311, p. 669-71.

344. Serrano, M. The tumor suppressor protein pl6INK4a.l997, Exp Cell Res, v. 237, p. 7-13.

345. Serrano, M., G. J. Hannon and D. Beach. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.1993, Nature, v. 366, p. 704-7.

346. Shah, G. Why do we still use serum in the production of biopharmaceuticals?1999, Dev Biol Stand, v. 99, p. 17-22.

347. Sharpless, N. E., N. Bardeesy, К. H. Lee, D. Carrasco, D. H. Castrillon, A. J. Aguirre, E. A. Wu, J. W. Horner and R. A. DePinho. Loss of pl6Ink4a with retention of pl9Arf predisposes mice to tumorigenesis.2001, Nature, v. 413, p. 86-91.

348. Shaulian, E. and M. Karin. AP-1 in cell proliferation and survival.2001, Oncogene, v. 20, p. 2390-400.

349. Shaulian, E. and M. Karin. AP-1 as a regulator of cell life and death.2002, Nat Cell Biol, v. 4, p. E131-6.

350. Shay, J. W., О. M. Pereira-Smith and W. E. Wright. A role for both RB and p53 in the regulation of human cellular senescence. 1991, Exp Cell Res, v. 196, p. 33-9.

351. Sheaff, R. J., M. Groudine, M. Gordon, J. M. Roberts and В. E. Clurman. Cyclin E-CDK2 is a regulator of p27Kip 1.1997. Genes Dev. v. 11, p. 1464-78.

352. Sherr, C. J. and J. M. Roberts. Inhibitors of mammalian G1 cyclin-dependent kinases.1995, Genes Dev. v. 9, p. 1149-63.

353. Shi, E., M. Kan, J. Xu, F. Wang, J. Hou and W. L. McKeehan. Control of fibroblast growth factor receptor kinase signal transduction by heterodimerization of combinatorial splice variants. 1993, Mol Cell Biol, v. 13, p. 3907-18.

354. Shimizu, M., E. Ichikawa, U. Inoue, T. Nakamura, T. Nakajima, H. Nojima, H. Okayama and K. Oda. The Gl/S boundary-specific enhancer of the rat cdc2 promoter. 1995, Mol Cell Biol, v. 15, p. 2882-92.

355. Shimokado, К., E. W. Raines, D. K. Madtes, Т. B. Barrett, E. P. Benditt and R. Ross. A significant part of macrophage-derived growth factor consists of at least two forms of PDGF.1985, СеП, v. 43, p. 277-86.

356. Shiozaki, С., K. Tashiro, M. Asano-Miyoshi, K. Saigo, Y. Emori and K. Shiokawa. Cloning of cDNA and genomic DNA encoding fibroblast growth factor receptor-4 of Xenopus laevis.1995, Gene, v. 152, p. 215-9.

357. Shute, J., L. Marshall, K. Bodey and A. Bush. Growth factors in cystic fibrosis when more is not enough.2003, Paediatr Respir Rev, v. 4, p. 120-7.

358. Sieff, C. A. Hematopoietic cell proliferation and differentiation. 1994, Curr Opin Hematol. v. 1, p. 310-20.

359. Silver, B. J., F. E. Jaffer and H. E. Abboud. Platelet-derived growth factor synthesis in mesangial cells: induction by multiple peptide mitogens. 1989, Proc Natl Acad Sci USA, v. 86, p. 1056-60.

360. Skolnik, E. Y., A. Batzer, N. Li, С. H. Lee, E. Lowenstein, M. Mohammadi, B. Margolis and J. Schlessinger. The function of GRB2 in linking the insulin receptor to Ras signaling pathways. 1993, Science, v. 260, p. 1953-5.

361. Smith, E. J., G. Leone and J. R. Nevins. Distinct mechanisms control the accumulation of the Rb-related pl07 and pl30 proteins during cell growth.1998, Cell Growth Differ, v. 9, p. 297-303.

362. Smith, M. L., I. Т. Chen, Q. Zhan, I. Bae, C. Y. Chen, Т. M. Gilmer, M. B. Kastan, P. M. O'Connor and A. J. Fomace, Jr. Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. 1994, Science, v. 266, p. 1376-80.

363. Soker, S., С. M. Svahn and G. Neufeld. Vascular endothelial growth factor is inactivated by binding to alpha 2-macroglobulin and the binding is inhibited by heparin. 1993, J Biol Chem. v. 268, p. 7685-91.

364. Solomon, M. J., J. W. Harper and J. Shuttleworth. CAK, the p34cdc2 activating kinase, contains a protein identical or closely related to p40M015.1993, Embo J. v. 12, p. 3133-42.

365. Soma, Y., V. Dvonch and G. R. Grotendorst. Platelet-derived growth factor AA homodimer is the predominant isoform in human platelets and acute human wound fluid. 1992, FasebJ, v. 6, p. 2996-3001.

366. Somasundaram, R. and D. Schuppan. Type I, II, III, IV, V, and VI collagens serve as extracellular ligands for the isoforms of platelet-derived growth factor (АА, BB, and AB).1996, J Biol Chem. v. 271, p. 26884-91.

367. Soriano, P. Abnormal kidney development and hematological disorders in PDGF beta-receptor mutant mice. 1994, Genes Dev. v. 8, p. 1888-96.

368. Soriano, P. The PDGF alpha receptor is required for neural crest cell development and for normal patterning of the somites. 1997, Development, v. 124, p. 2691-700.

369. Sorokin, A., M. Mohammadi, J. Huang and J. Schlessinger. Internalization of fibroblast growth factor receptor is inhibited by a point mutation at tyrosine 766.1994, J Biol Chem. v. 269, p. 17056-61.

370. Soucek, Т., О. Pusch, E. Hengstschlager-Ottnad, P. D. Adams and M. Hengstschlager. Deregulated expression of E2F-1 induces cyclin A- and E-associated kinase activities independently from cell cycle position. 1997, Oncogene, v. 14, p. 2251-7.

371. Stachowiak, M. K., J. Moffett, P. Maher, J. Tucholski and E. K. Stachowiak. Growth factor regulation of cell growth and proliferation in the nervous system. A new intracrine nuclear mechanism. 1997, Mol Neurobiol. v. 15, p. 257-83.

372. Stein, G. H. and L. Atkins. Membrane-associated inhibitor of DNA synthesis in senescent human diploid fibroblasts: characterization and comparison to quiescent cell inhibitor.1986, Proc Natl Acad Sci USA, v. 83, p. 9030-4.

373. Stein, G. H., L. F. Drullingcr, R. S. Robetorye, О. M. Pereira-Smith and J. R. Smith. Senescent cells fail to express cdc2, cycA, and cycB in response to mitogen stimulation. 1991, Proc Natl Acad Sci USA, v. 88, p. 11012-6.

374. Stein, G. H., L. F. Drullinger, A. Soulard and V. Dulic. Differential roles for cyclin-dependent kinase inhibitors p21 and pi 6 in the mechanisms of senescence and differentiation in human fibroblasts. 1999, Mol Cell Biol, v. 19, p. 2109-17.

375. Stiles, С. D., G. Т. Caponc, С. D. Scher, H. N. Antoniadcs, J. J. Van Wyk and W. J. Pledger. Dual control of cell growth by somatomedins and platelet-derived growth factor. 1979, Proc Natl Acad Sci USA, v. 76, p. 1279-83.

376. Stiles, C. D., W. J. Pledger, R. W. Tucker, R. G. Martin and C. D. Scher. Regulation of the Balb/c-3T3 cell cycle-effects of growth factors.1980, J Supramol Struct, v. 13, p. 489-99.

377. Straus, D. S. Growth-stimulatory actions of insulin in vitro and in vivo. 1984, Endocr Rev, v. 5, p. 356-69.

378. Strausfeld, U., J. C. Labbe, D. Fesquet, J. C. Cavadore, A. Picard, K. Sadhu, P. Russell and M. Doree. Dephosphorylation and activation of a p34cdc2/cyclin В complex in vitro by human CDC25 protein. 1991, Nature, v. 351, p. 242-5.

379. Stremmel, W., L. Pohl, A. Ring and T. Herrmann. A new concept of cellular uptake and intracellular trafficking of long-chain fatty acids.2001, Lipids, v. 36, p. 981-9.

380. Strobeck, M. W., К. E. Knudsen, A. F. Fribourg, M. F. DeCristofaro, В. E. Weissman, A. N. Imbalzano and E. S. Knudsen. BRG-1 is required for RB-mediated cell cycle arrest.2000, Proc Natl Acad Sci USA, v. 97, p. 7748-53.

381. Strober, В. E., J. L. Dunaicf, Guha and S. P. Goff. Functional interactions between the hBRM/hBRGl transcriptional activators and the pRB family of proteins.1996, Mol Cell Biol, v. 16, p. 1576-83.

382. Sturani, E., L. Toschi, R. Zippel, E. Martegani and L. Alberghina. G1 phase heterogeneity in exponentially growing Swiss 3T3 mouse fibroblasts.1984, Exp Cell Res, v. 153, p. 135-44.

383. Suzuki, Т., H. Okuno, T. Yoshida, T. Endo, H. Nishina and H. Iba. Difference in transcriptional regulatory function between c-Fos and Fra-2.1991, Nucleic Acids Res, v. 19, p. 5537-42.

384. Takeda, Т., M. Hosokawa and K. Higuchi. Senescence-accelerated mouse (SAM): a novel murine model of senescence. 1997, Exp Gerontol, v. 32, p. 105-9.

385. Takenaka, H., S. Kishimoto, I. Tooyama, H. Kimura and H. Yasuno. Protein expression of fibroblast growth factor receptor-1 in keratinocytes during wound healing in rat skin. 1997, J Invest Dermatol, v. 109, p. 108-12.

386. Taketani, Y. and T. Oka. Epidermal growth factor stimulates cell proliferation and inhibits functional differentiation of mouse mammary epithelial cells in culture.1983, Endocrinology, v. 113, p. 871-7.

387. Tan, С. К., C. Castillo, A. G. So and К. M. Downey. An auxiliary protein for DNA polymerase-delta from fetal calf thymus.1986, J Biol Chem, v. 261, p. 12310-6.

388. Tanaka, E. M., D. N. Drechsel and J. P. Brockes. Thrombin regulates S-phase re-entry by cultured newt myotubes.1999, Curr Biol, v. 9, p. 792-9.

389. Taya, Y. RB kinases and RB-binding proteins: new points of view. 1997, Trends Biochem Sci. v. 22, p. 14-7.

390. Terada, Y., M. Tatsuka, S. Jinno and H. Okayama. Requirement for tyrosine phosphorylation of Cdk4 in G1 arrest induced by ultraviolet irradiation. 1995, Nature, v. 376, p. 358-62.

391. Thomson, J. A., J. Itskovitz-Eldor, S. S. Shapiro, M. A. Waknitz, J. J. Swiergiel, V. S. Marshall and J. M. Jones. Embryonic stem cell lines derived from human blastocysts. 1998, Science, v. 282, p. 1145-7.

392. Thyberg, J. and В. B. Fredholm. Modulation of arterial smooth muscle cells from contractile to synthetic phenotype requires induction of ornithine decarboxylase activity and polyamine synthesis.1987, Exp Cell Res, v. 170, p. 153-9.

393. Tomoda, K., Y. Kubota and J. Kato. Degradation of the cyclin-dependent-kinase inhibitor p27Kipl is instigated by Jabl.1999, Nature, v. 398, p. 160-5.

394. Tsurimoto, T. PCNA binding proteins. 1999, Front Biosci. v. 4, p. D849-58.

395. Umar, A., A. B. Buermeyer, J. A. Simon, D. C. Thomas, A. B. Clark, R. M. Liskay and T. A. Kunkel. Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis.1996, СеП, v. 87, p. 65-73.

396. Vairo, G., D. M. Livingston and D. Ginsberg. Functional interaction between E2F-4 and pl30: evidence for distinct mechanisms underlying growth suppression by different retinoblastoma protein family members. 1995, Genes Dev. v. 9, p. 869-81.

397. Vaziri, H. and S. Benchimol. Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span. 1998, Curr Biol, v. 8, p. 27982.

398. Verona, R., K. Moberg, S. Estes, M. Starz, J. P. Vernon and J. A. Lees. E2F activity is regulated by cell cycle-dependent changes in subcellular localization. 1997, Mol Cell Biol, v. 17, p. 7268-82.

399. Vlach, J., S. Hennecke and B. Amati. Phosphorylation-dependent degradation of the cyclin-dependent kinase inhibitor p27.1997, Embo J, v. 16, p. 5334-44.

400. Vlodavsky, I., H. Q. Miao, B. Medalion, P. Danagher and D. Ron. Involvement of heparan sulfate and related molecules in sequestration and growth promoting activity of fibroblast growth factor. 1996, Cancer Metastasis Rev, v. 15, p. 177-86.

401. Vogel, A., E. Raines, B. Kariya, M. J. Rivest and R. Ross. Coordinate control of 3T3 cell proliferation by platelet-derived growth factor and plasma components. 1978, Proc Natl Acad Sci USA, v. 75, p. 2810-4.

402. Wagner, A. J., C. Meyers, L. A. Laimins and N. Hay. c-Myc induces the expression and activity of ornithine decarboxylase. 1993, Cell Growth Differ, v. 4, p. 879-83.

403. Wagner, M., B. Hampel, E. Hutter, G. Pfister, W. Krek, W. Zwerschke and P. Jansen-Durr. Metabolic stabilization of p27 in senescent fibroblasts correlates with reduced expression of the F-box protein Skp2.2001, Exp Gerontol, v. 37, p. 41-55.

404. Waltenberger, J. Modulation of growth factor action: implications for the treatment of cardiovascular diseases. 1997, Circulation, v. 96, p. 4083-94.

405. Walz, A., S. McFarlane, Y. G. Brickman, V. Nurcombe, P. F. Bartlett and С. E. Holt. Essential role of heparan sulfates in axon navigation and targeting in the developing visual system. 1997, Development, v. 124, p. 2421-30.

406. Wang, D., S. Yamamoto, N. Hijiya, E. N. Benveniste and C. L. Gladson. Transcriptional regulation of the human osteopontin promoter: functional analysis and DNA-protein interactions.2000, Oncogene, v. 19, p. 5801-9.

407. Wang, F., M. Kan, J. Xu, G. Yan and W. L. McKeehan. Ligand-specific structural domains in the fibroblast growth factor receptor. 1995, J Biol Chem. v. 270, p. 10222-30.

408. Welshons, W. V., L. H. Grady, K. S. Engler and В. M. Judy. Control of proliferation of MCF-7 breast cancer cells in a commercial preparation of charcoal-stripped adult bovine serum. 1992, Breast Cancer Res Treat, v. 23, p. 97-104.

409. Werner, S., K. G. Peters, M. T. Longaker, F. Fuller-Pace, M. J. Banda and L. T. Williams. Large induction of keratinocyte growth factor expression in the dermis during wound healing. 1992, Proc Natl Acad Sci USA, v. 89, p. 6896-900.

410. Westermark, B. and A. Wasteson. A platelet factor stimulating human normal glial cells. 1976, Exp Cell Res, v. 98, p. 170-4.

411. Wiedlocha, A., P. O. Falnes, A. Rapak, O. Klingenberg, R. Munoz and S. Olsnes. Translocation of cytosol of exogenous, CAAX-tagged acidic fibroblast growth factor. 1995, J Biol Chem. v. 270, p. 30680-5.

412. Witte, L. D., K. L. Kaplan, H. L. Nossel, B. A. Lages, H. J. Weiss and D. S. Goodman. Studies of the release from human platelets of the growth factor for cultured human arterial smooth muscle cells. 1978, С ire Res, v. 42, p. 402-9.

413. Woo, M. S., I. Sanchez and B. D. Dynlacht. pi30 and pi07 use a conserved domain to inhibit cellular cyclin-dependent kinase activity. 1997, Mol Cell Biol, v. 17, p. 3566-79.

414. Wright, W. E., О. M. Pereira-Smith and J. W. Shay. Reversible cellular senescence: implications for immortalization of normal human diploid fibroblasts. 198 9, Mol Cell Biol, v. 9, p. 3088-92.

415. Wu, Y., H. Huang, Z. Miner and M. Kulesz-Martin. Activities and response to DNA damage of latent and active sequence-specific DNA binding forms of mouse p53.1997, Proc Natl Acad Sci USA, v. 94, p. 8982-7.

416. Xiong, Y., H. Zhang and D. Beach. D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA.1992, Cell, v. 71, p. 505-14.

417. Xu, M., K. A. Sheppard, C. Y. Peng, A. S. Yee and H. Piwnica-Worms. Cyclin A/CDK2 binds directly to E2F-1 and inhibits the DNA-binding activity of E2F-1/DP-1 by phosphorylation. 1994. Mol Cell Biol, v. 14, p. 8420-31.

418. Yamasaki, M., A. Miyake, S. Tagashira and N. Itoh. Structure and expression of the rat mRNA encoding a novel member of the fibroblast growth factor family. 1996, J Biol Chem. v. 271, p. 15918-21.

419. Yamashiro, S., Y. Yamakita, H. Hosoya and F. Matsumura. Phosphorylation of non-muscle caldesmon by p34cdc2 kinase during mitosis. 1991, Nature, v. 349, p. 169-72.

420. Yang, J., E. Chang, A. M. Cherry, C. D. Bangs, Y. Oei, A. Bodnar, A. Bronstein, C. P. Chiu and G. S. Herron. Human endothelial cell life extension by telomerase expression. 1999, J Biol Chem. v. 274, p. 26141-8.

421. Yang, R., R. Morosetti and H. P. Koeffler. Characterization of a second human cyclin A that is highly expressed in testis and in several leukemic cell lines. 1997, Cancer Res, v. 57, p. 913-20.

422. Yeh, H. J., K. G. Ruit, Y. X. Wang, W. C. Parks, W. D. Snider and T. F. Deuel. PDGF A-chain gene is expressed by mammalian neurons during development and in maturity. 1991, Cell, v. 64, p. 209-16.

423. Yeoman, L. C. An autocrine model for cell- and matrix-associated fibroblast growth factor. 1993, Oncol Res, v. 5, p. 489-99.

424. Yiangou, C., J. J. Gomm, R. С. Coope, M. Law, Y. A. Luqmani, S. Shousha, R. C. Coombes and C. L. Johnston. Fibroblast growth factor 2 in breast cancer: occurrence and prognostic significance.1997, Br J Cancer, v. 75, p. 28-33.

425. Young, D. V. and M. C. Dean. The suppression of cellular proliferation in SV40-transformed 3T3 cells by glucocorticoids. 1980, J Cell Physiol, v. 102, p. 223-31.

426. Zhan, X., X. Hu, R. Friesel and T. Maciag. Long term growth factor exposure and differential tyrosine phosphorylation are required for DNA synthesis in BALB/c 3T3 cells. 1993, J Biol Chem. v. 268, p. 9611-20.

427. Zhang, H. S., M. Gavin, A. Dahiya, A. A. Postigo, D. Ma, R. X. Luo, J. W. Harbour and D. C. Dean. Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF.2000, СеЦ, v. 101, p. 79-89.

428. Zhang, Y. and D. E. Wilcox. Thermodynamic and spectroscopic study of Cu(II) and Ni(II) binding to bovine serum albumin.2002, J Biol Inorg Chem. v. 7, p. 327-37.

429. Zhou, B. P., Y. Liao, W. Xia, B. Spohn, M. H. Lee and M. C. Hung. Cytoplasmic localization of p21Cipl/WAFl by Akt-induced phosphorylation in HER-2/neu-overexpressing cells.2001.Nat Cell Biol, v. 3, p. 245-52.

430. Zieske, J. D. Expression of cyclin-dependent kinase inhibitors during corneal wound repair.2000, Prog Retin Eve Res, v. 19, p. 257-70.

431. Zindy, F., J. van Deursen, G. Grosveld, C. J. Sherr and M. F. Roussel. INK4d-deficient mice are fertile despite testicular atrophy.2000, Mol Cell Biol, v. 20, p. 372-8.1. БЛАГОДАРНОСТИ