Insulin-induced cell cycle progression is impaired in chinese hamster ovary cells overexpressing insulin receptor substrate-3

Endocrinology
Yasushi KaburagiYoshio Yazaki

Abstract

To analyze the roles of insulin receptor substrate (IRS) proteins in insulin-stimulated cell cycle progression, we examined the functions of rat IRS-1 and IRS-3 in Chinese hamster ovary cells overexpressing the human insulin receptor. In this type of cell overexpressing IRS-1 or IRS-3, we showed that: 1) overexpression of IRS-3, but not IRS-1, suppressed the G1/S transition induced by insulin; 2) IRS-3 was more preferentially localized to the nucleus than IRS-1; 3) phosphorylation of glycogen synthase kinase 3 and MAPK/ERK was unaffected by IRS-3 overexpression, whereas that of protein kinase B was enhanced by either IRS; 4) overexpressed IRS-3 suppressed cyclin D1 expression in response to insulin; 5) among the signaling molecules regulating cyclin D1 expression, activation of the small G protein Ral was unchanged, whereas insulin-induced gene expression of c-myc, a critical component for growth control and cell cycle progression, was suppressed by overexpressed IRS-3; and 6) insulin-induced expression of p21, a cyclin-dependent kinase inhibitor, was decreased by overexpressed IRS-3. These findings imply that: 1) IRS-3 may play a unique role in mitogenesis by inhibiting insulin-stimulated cell cycle progression via a decrease ...Continue Reading

References

Sep 14, 1995·Nature·X J SunM F White
May 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·L M WangS A Aaronson
Mar 15, 1997·Genes & Development·S G KennedyN Hay
Apr 1, 1997·Genes & Development·J LaBaerE Harlow
Nov 5, 1997·Endocrinology·S Sciacchitano, S I Taylor
Mar 14, 1998·Proceedings of the National Academy of Sciences of the United States of America·M ChengM F Roussel
Mar 12, 1998·Nature·D J WithersM F White
Jul 25, 1998·The Biochemical Journal·P R ShepherdK Siddle
Aug 26, 1998·Proceedings of the National Academy of Sciences of the United States of America·G F Hu
Apr 9, 1999·The Journal of Clinical Investigation·A VirkamäkiC R Kahn
Jun 11, 1999·The Journal of Biological Chemistry·S C LiuS R Keller
Jul 1, 1999·Genes & Development·C J Sherr, J M Roberts
Jul 15, 1999·Biochemical and Biophysical Research Communications·V R FantinL M Wang
Oct 26, 1999·The Journal of Biological Chemistry·B H QuD LeRoith
Dec 22, 1999·Current Opinion in Cell Biology·C Marshall
Jan 25, 2000·American Journal of Physiology. Endocrinology and Metabolism·V R FantinS R Keller
Feb 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·H HermekingK W Kinzler
Dec 13, 2000·Molecular and Cellular Biology·K TsuruzoeC R Kahn
Feb 27, 2001·FEBS Letters·S NasiL Soucek
May 29, 2001·Molecular Pathology : MP·B Valentinis, R Baserga
Oct 20, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G SestiR Lauro
Nov 29, 2001·The Journal of Biological Chemistry·Tomohiro KabutaShin-Ichiro Takahashi
Jan 24, 2002·The Journal of Biological Chemistry·Rosalie C Sears, Joseph R Nevins
Aug 10, 2002·American Journal of Physiology. Endocrinology and Metabolism·Morris F White
Dec 31, 2002·Biochemical and Biophysical Research Communications·Yasushi KaburagiYoshio Yazaki
Mar 5, 2003·Journal of Cell Science·Bradley W Doble, James R Woodgett

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Citations

Jun 12, 2012·Endocrine-related Cancer·Henning HvidMichael Pollak
Mar 17, 2010·Biochemical and Biophysical Research Communications·Tomohiro KabutaShin-Ichiro Takahashi
Jun 8, 2007·The Journal of Biological Chemistry·Keertik FulzeleThomas L Clemens

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