Tyrosine phosphorylation of p85 relieves its inhibitory activity on phosphatidylinositol 3-kinase

The Journal of Biological Chemistry
B D CuevasG B Mills

Abstract

Under resting conditions, the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K) serves to both stabilize and inactivate the p110 catalytic subunit. The inhibitory activity of p85 is relieved by occupancy of the NH(2)-terminal SH2 domain of p85 by phosphorylated tyrosine. Src family kinases phosphorylate tyrosine 688 in p85, a process that we have shown to be reversed by the activity of the p85-associated SH2 domain-containing phosphatase SHP1. We demonstrate that phosphorylation of the downstream PI3K target Akt is increased in cells lacking SHP1, implicating phosphorylation of p85 in the regulation of PI3K activity. Furthermore, the in vitro specific activity of PI3K associated with tyrosine- phosphorylated p85 is higher than that associated with nonphosphorylated p85. Expression of wild-type p85 inhibits PI3K enzyme activity as indicated by PI3K- dependent Akt phosphorylation. The inhibitory activity of p85 is accentuated by mutation of tyrosine 688 to alanine and reversed by mutation of tyrosine 688 to aspartic acid, changes that block and mimic tyrosine phosphorylation, respectively Strikingly, mutation of tyrosine 688 to aspartic acid completely reverses the inhibitory activity of p85 on cell viability and act...Continue Reading

References

Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·W Huang, R L Erikson
Aug 1, 1998·The Journal of Biological Chemistry·M Pap, G M Cooper
Nov 13, 1998·Science·M H CardoneJ C Reed
Dec 5, 1998·Biochimica Et Biophysica Acta·M P Wymann, L Pirola
Mar 20, 1999·The Journal of Biological Chemistry·L E Rameh, L C Cantley
Apr 23, 1999·The Journal of Biological Chemistry·A G HarpurM D Waterfield
Sep 17, 1999·The Journal of Biological Chemistry·B CuevasG B Mills
Jun 3, 2000·Annual Review of Immunology·M Karin, Y Ben-Neriah

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Citations

Jun 22, 2006·Apoptosis : an International Journal on Programmed Cell Death·Kerstin BellmannJacques Landry
Apr 18, 2006·Nature Medicine·Marie-Julie DuboisAndré Marette
Oct 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·Akiyoshi UezuScott H Soderling
Jun 11, 2009·The Journal of Biological Chemistry·Genqing LiangKirk M Druey
Apr 5, 2011·The Journal of Biological Chemistry·Julie ToubianaJean-Daniel Chiche
Jul 7, 2005·Antioxidants & Redox Signaling·Mohamad Z MehdiAshok K Srivastava
Jun 29, 2007·Molecular Biology of the Cell·Shirin KazemiAntonis E Koromilas
Aug 5, 2011·Molecular Biology of the Cell·James R WhitefordJohn R Couchman
Oct 20, 2011·Science Signaling·Oscar VadasRoger L Williams
Jan 20, 2004·Molecular and Cellular Biology·Lazaros C FoukasPeter R Shepherd
Feb 7, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Anna GatesCynthia R L Webster
Oct 6, 2005·American Journal of Physiology. Renal Physiology·Dimin LiWen-Hui Wang
May 4, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John J ArcaroliWells A Messersmith
Mar 18, 2009·Journal of Leukocyte Biology·Michelle H W LairdStefanie N Vogel
Sep 9, 2011·Molecular Biology of the Cell·Maria LodeiroJesus P Camiña
Apr 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Qing ZhangJennifer Rubin Grandis
May 27, 2014·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Sekhar PalAmitava Chatterjee
Feb 11, 2015·The Journal of Cell Biology·Heath E JohnsonJason M Haugh
Jan 26, 2016·Pharmacogenomics·Lydia Wt Cheung, Gordon B Mills
Dec 24, 2013·Clinical Colorectal Cancer·Jiezhong ChenM Wasif Saif
Jul 23, 2013·Frontiers in Neuroendocrinology·Marily Theodoropoulou, Günter K Stalla
Mar 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Raven J ReddyForest M White
Apr 15, 2006·The Journal of Investigative Dermatology·John A CurtinBoris C Bastian
Oct 7, 2008·Biochemical and Biophysical Research Communications·Daniel SaganHedda Eichholtz-Wirth
Sep 9, 2008·Trends in Immunology·Mi-Sun KimAlasdair M Gilfillan

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