Sam68 is a docking protein linking GAP and PI3K in insulin receptor signaling

Molecular and Cellular Endocrinology
V Sánchez-Margalet, S Najib

Abstract

The 68 kDa Src substrate associated during mitosis (Sam68) is an RNA binding protein with Src homology (SH) 2 and 3 domain binding sites. We have recently found that Sam68 is a substrate of the insulin receptor (IR) and that Tyr-phosphorylated Sam68 associates with the SH2 domains of p85 PI3K. In the present work, using HTC-IR cells, we have found that insulin stimulation promotes the relocalization of Sam68 from the nucleus to the cytoplasm, and we have further studied the role of Sam68 in insulin receptor signaling complexes, by co-precipitating experiments. Thus, Sam68 is co-precipitated with p85 PI3K, IRS-1 and IR. The association of Sam68 with these complexes is mediated by the SH2 domains of PI3K. Moreover, we have found that Sam68 is a p120GAP associated protein after Tyr-phosphorylation by the IR. This association is mediated by the SH2 domains of GAP (preferentially the C-terminal SH2). Thus, Sam68 is linking p120GAP to PI3K signaling pathway. In fact, PI3K activity was increased in both anti-Sam68 and anti-GAP immmunoprecipitates upon insulin stimulation. We propose that the recruitment of the docking protein Sam68 to the PI3K pathway may serve to allow the association of other signaling molecules, i.e. p120GAP. In th...Continue Reading

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Citations

Dec 4, 2003·Biochimica Et Biophysica Acta·Kiven E Lukong, Stéphane Richard
Jan 14, 2009·Molecular and Cellular Biology·Marc-Etienne HuotStéphane Richard
Nov 30, 2013·International Journal of Molecular Sciences·Flora Sánchez-Jiménez, Víctor Sánchez-Margalet
Oct 12, 2007·Future Oncology·Kiven E Lukong, Stéphane Richard
Jul 12, 2002·Journal of Cellular Biochemistry·Souad Najib, Víctor Sánchez-Margalet
Mar 19, 2014·Protein & Cell·Yipeng Du, Taotao Wei
Oct 19, 2011·Biochemical Pharmacology·R Quintana-PortilloC González-Yanes
Apr 10, 2016·Biochemical and Biophysical Research Communications·Weijie WuYouhua Wang
Nov 3, 2010·Molecular and Cellular Endocrinology·Flora Sánchez-JiménezVíctor Sánchez-Margalet
Jul 16, 2016·PloS One·Antonio Pérez-PérezVíctor Sánchez-Margalet
Mar 18, 2015·Biological Chemistry·Anne HennigIgnacio Rubio
Mar 1, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·Z LiL-B Song
Sep 15, 2007·Cellular Signalling·Galit LazerShulamit Katzav

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