The insulin receptor substrate (IRS)-1 recruits phosphatidylinositol 3-kinase to Ret: evidence for a competition between Shc and IRS-1 for the binding to Ret

Oncogene
Rosa Marina MelilloM Santoro

Abstract

Tyrosine 1062 of Ret, which represents an intracytoplasmic docking site for multiple signaling molecules, is essential for Ret-mediated activation of phosphatidylinositol 3-Kinase (PI3-K). PI3-K, in turn, has been implicated in inducing cell survival and neoplastic transformation mediated by Ret. We have examined the mechanisms by which Ret stimulates PI3-K. Here we show that the Insulin Receptor Substrate-1 (IRS-1) is tyrosine phosphorylated and associated with the p85 regulatory subunit of PI3-K in response to Ret activation. IRS-1 coimmunoprecipitates with Ret and co-expression of IRS-1 results in the potentiation of Ret-mediated activation of Akt(PKB), a bona fide effector of PI3-K. The association with the PTB domain of IRS-1 depends on the phosphorylation of tyrosine 1062 of Ret. The deletion of asparagine 1059 (delN1059) and the substitution of leucine 1061 (L1061P), two Ret mutations identified in families affected by congenital megacolon (Hirschsprung's disease), impair the binding of IRS-1 to Ret as well as Ret-mediated Akt(PKB) stimulation. Finally, we show that Shc, which was previously identified as another ligand of Y1062 of Ret, competes with IRS-1 for the binding to Ret pY1062. All together, these findings sugge...Continue Reading

References

Nov 17, 1995·The Journal of Biological Chemistry·G WolfS E Shoelson
Jun 1, 1995·Mammalian Genome : Official Journal of the International Mammalian Genome Society·F CanzianI Ceccherini
Sep 15, 1995·The Journal of Biological Chemistry·A PandeyV M Dixit
Jul 1, 1993·Trends in Biotechnology·A Prokop
Jul 1, 1995·Molecular and Cellular Biology·B MatoskovaP P Di Fiore
Feb 1, 1994·Current Opinion in Genetics & Development·J Schlessinger
Aug 1, 1993·Trends in Biochemical Sciences·J Schlessinger
Apr 1, 1996·Nature Structural Biology·M M ZhouS W Fesik
Apr 1, 1996·Trends in Genetics : TIG·B PasiniG Romeo
Feb 20, 1997·Oncogene·E ArighiM G Borrello
Feb 12, 1998·Science·T Pawson, J D Scott
Apr 7, 1998·Molecular and Cellular Biology·K DurickS S Taylor
Oct 9, 1998·Oncogene·L AlbertiM A Pierotti
Jan 14, 1999·Nature Structural Biology·G Siegal
Mar 20, 1999·The Journal of Biological Chemistry·L E Rameh, L C Cantley
Jun 5, 1999·Molecular and Cellular Neurosciences·M S AiraksinenM Saarma

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Citations

Jun 12, 2002·Biochemical and Biophysical Research Communications·Naoko IwahashiMasahide Takahashi
Oct 5, 2001·Trends in Genetics : TIG·S ManiéM Billaud
Sep 20, 2006·Molecular and Cellular Biology·Matthew J SmithTony Pawson
Sep 2, 2004·Molecular and Cellular Biology·Mayumi JijiwaMasahide Takahashi
May 21, 2003·Journal of Internal Medicine·K KurokawaM Takahashi
Aug 1, 2007·Journal of Neurochemistry·Jason A GustinJeffrey Milbrandt
Sep 8, 2004·Biochemical and Biophysical Research Communications·Kengo MaedaMasahide Takahashi
Jun 29, 2005·Cytokine & Growth Factor Reviews·Elena ArighiHannu Sariola
Aug 15, 2002·Biochemical and Biophysical Research Communications·Maria Grazia BorrelloMarco A Pierotti
Mar 4, 2015·Cancer·Jason D Prescott, Martha A Zeiger
Feb 16, 2002·Developmental Biology·Ming-Jer TangGregory R Dressler
Oct 23, 2003·The Journal of Biological Chemistry·Nobuhide KoboriPramod K Dash
Feb 10, 2004·The Journal of Biological Chemistry·Mario EncinasEugene M Johnson
Nov 19, 2005·Journal of Neuroscience Research·Rebecca Hui Kwan LeeSiu Yuen Chan
Jun 28, 2002·The Journal of Biological Chemistry·Hideki MurakamiMasahide Takahashi
Mar 12, 2002·The Journal of Biological Chemistry·Toshifumi FukudaMasahide Takahashi
Nov 6, 2001·The Journal of Biological Chemistry·Matthew N PoySonia M Najjar
Jul 2, 2002·The Journal of Biological Chemistry·Brian A Tsui-PierchalaEugene M Johnson
Mar 26, 2003·Journal of Cellular Physiology·Luisella AlbertiMarco A Pierotti
Jul 20, 2006·Endocrine Reviews·Jan Willem B de GrootRobert M W Hofstra
May 27, 2016·The Journal of Biological Chemistry·Nicole A GabreskiBrian A Pierchala
Jul 4, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anna TamburrinoMassimo Santoro
Jul 3, 2004·Cancer Research·Shirley M Myers, Lois M Mulligan
Aug 3, 2004·The Journal of Biological Chemistry·Robert J CrowderJeffrey Milbrandt
Nov 11, 2003·The Journal of Biological Chemistry·Ning ShiZihe Rao

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