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1999 | 46 | 1 |

Tytuł artykułu

Insulin-like growth factor I activates insulin receptor substrate 1 and Ras in human osteosarcoma cells

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Insulin-like growth factor I (IGF-I) stimulates multiplication of the human osteosarcoma cell line, MG-63, by acting through IGF-I receptor. We have characterized IGF-I stimulated phosphorylation of IRS-1, activation of Ras cycle and phosphorylation of c-Jun in this cell line. Serum starved MG-63 cells were (1) IGF-I stimulated and lysates were immunoprecipitated with polyclonal IRS-1 antibody or (2) metabolically labeled with [32P]orthophosphoric acid and then cells were treated with IGF-I. Cell lysates were immunoprecipitated with p21Ras antibody(Y13-259) and bound nucleotides were analysed by thin layer chromatography. We demonstrated tyrosine phosphorylation of IRS-1/2 immunoprecipitated from MG-63 cells stimulated with IGF-I. We also showed an increased level of GTP in p21Ras immunoprecipitates from IGF-I treated cells. Nuclear extracts prepared from 32P-labeled cells before and after addition of IGF-I were immunoprecipitated with c-Jun antibody. After electrophoresis and autoradiography, phosphorylation of the c-Jun band was seen to be IGF-I independent. Phosphoamino acid analysis of the c-Jun band showed that phosphoserine was the major species.

Wydawca

-

Rocznik

Tom

46

Numer

1

Opis fizyczny

p.117-123,fig.

Twórcy

  • National Cancer Institute, Bethesda, Maryland 20892-1374, USA
autor

Bibliografia

  • 1. Chan, J.M., Stampfer, M.J., Giovannucci, E., Gann, P.H., Ma, J., Wilkinson, P., Honne- kens, C.H. & Pollack, M. (1998) Plasma insulin-like growth factor-I and prostate can­cer risk: A prospective study. Science, 279,563-566.
  • 2. Hankinson, S.E., Willett, W.C., Colditz, G.A., Hunter, D.J., Michaud, D.S., Deroo, B., Ros- ner., B., Speizel, F.E. & Pollack, M. (1998) Cir­culating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351, 1393-1396.
  • 3. Werner, H. & LeRoith, D. (1997) The insulin­like growth factor-I receptor signaling path­ways are important for tumorgenesis and in­hibition of apoptosis. Crit. Rev. Oncogen. 8, 71-92.
  • 4. Furlanetto, R.W., HarweU, S.E. & Frick, K.K. (1994) Insulin-like growth factor-I induces cyclin-Dl expression in MG63 human osteo­sarcoma cells in vitro. Moi Endocrinol. 8, 510-517.
  • 5. Furlanetto, R.W. (1988) Receptor-mediated endocytosis and lysosomal processing of insulin-like growth factor I by mitogenically responsive cells. Endocrinology 122, 2044-2053.
  • 6. Pollak, M.N., Polychronakos, C. & Richard, M. (1990) Insulin-like growth factor I: A potent mitogen for osteogenic sarcoma. J. Natl. Can­cer Inst. 82, 301-305.
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  • 10. Sun, X.J., Rothenberg, P., Kahn, C.R., Backer, J.M., Araki, E., Wilden, P.A., Cahill, D.A., Goldstein, B.J. & White, M.F. (1991) The structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature 352, 73-77.
  • 11. Myers, M.G., Backer, J.M., Sun, X.J., Shoel- son, S., Hu, P., Schlessinger, J., Yoakim, M., Schaffhausen, B. & White, M.F. (1992) IRS-1 activates the phosphatidylinositol 3'-kinase by associating with src homology 2 domains of p85. Proc. Natl. Acad. Scu U.S.A. 89, 10350- 10354.
  • 12. Pawson, T. & Scott, J.D. (1997) Signaling through scaffold, ancoring, and adaptor pro­teins. Science 278, 2075-2080.
  • 13. Karin, M. (1995) The regulation of AP-1 activ­ity by mitogen-activated protein kinases. J. Biol. Chem. 270, 16483-16486.
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  • 19. Lopaczynski, W., Harris, S. & Nissley, P. (1999) Activation of extracellular signal- regulated kinases ERK1 and ERK2 by insulin­like growth factor I in MG-63 cells. Horm. Me- tab. Res. (in press).
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  • 21. Yonezawa, K., Ando, A., Kaburagi, Y., Yamamoto-Honda, R., Kitamura, T., Hara, K., Nakafuku, M., Okabayashi, Y., Kadowaki, T., Kaziro, Y. & Kasuga, M. (1994) Signal trans­duction pathways from insulin receptors to Ras. Analysis by mutant insulin receptors. J. Rial Chem. 269, 4634-4640.
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  • 23. Neary, J.T. (1997) MAPK cascades in cell growth and death. News Physiol Sci. 12, 286-293.
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  • 25. Dey, B., Frick, K., Lopaczynski, W., Nissley, S.P. & Furnaletto, R. (1996) Evidence for di­rect interaction of the IGF-I receptor with IRS-1, She, and Grb-10. Mol Endocrinol. 10, 631-641.
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Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

bwmeta1.element.agro-article-57c1aa6b-f3b0-4660-83c8-70a58a1c2281
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