A function for phosphoinositide 3-kinase beta lipid products in coupling beta gamma to Ras activation in response to lysophosphatidic acid

The Journal of Biological Chemistry
A YartP Raynal

Abstract

Although Gbetagamma is thought to mediate mitogen-activated protein kinase (MAPK) activation in response to G protein-coupled receptor stimulation, the mechanisms involved in this pathway have not been clearly defined. Phosphoinositide 3-kinase (PI3K) has been proposed as an early intermediate in this process, but its role has remained elusive. We have observed that dominant negative mutants of p110beta, but not of p110gamma, inhibited MAPK stimulation in response to lysophosphatidic acid (LPA). The role of p110beta was located upstream from Ras. To determine which of the lipid or protein kinase activities of p110beta were important for Ras activation, we produced a mutant p110beta lacking the lipid but not the protein kinase activity. This protein displayed a dominant negative activity similar to a kinase-dead mutant, indicating that p110beta lipid kinase activity was essentially involved in Ras activation. In agreement, overexpression of the lipid phosphatase PTEN was found to specifically inhibit Ras stimulation induced by LPA. In addition, we have observed that the PH domain-containing adapter protein Gab1, which is involved in p110beta activation during LPA stimulation, is also implicated in this pathway downstream of p110...Continue Reading

References

Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·W J KochR J Lefkowitz
Jul 1, 1997·Trends in Biochemical Sciences·B VanhaesebroeckM D Waterfield
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·A AugustH Hanafusa
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·A HerrlichT Gudermann
Sep 5, 1998·JAMA : the Journal of the American Medical Association·Y XuG Casey
Oct 13, 1998·Current Biology : CB·M M ChouA Toker
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·M P MyersN K Tonks
Mar 20, 1999·The Journal of Biological Chemistry·L E Rameh, L C Cantley
Apr 21, 1999·Current Opinion in Cell Biology·S J LeeversM D Waterfield
Dec 2, 1999·Experimental Cell Research·W H Moolenaar
Dec 22, 1999·Trends in Pharmacological Sciences·K R Lynch, D S Im
Feb 10, 2000·Advances in Experimental Medicine and Biology·E J Goetzl, S An

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Citations

Oct 12, 2012·International Journal of Hematology·Fatemeh Moheimani, Denise E Jackson
May 15, 2003·Archives of Biochemistry and Biophysics·Lazaros C Foukas, Klaus Okkenhaug
Aug 7, 2003·Current Opinion in Pharmacology·Stephen G Ward, Peter Finan
Jun 12, 2008·Proceedings of the National Academy of Sciences of the United States of America·Julie Guillermet-GuibertBart Vanhaesebroeck
Dec 25, 2009·Journal of Neurophysiology·Kirill UkhanovBarry W Ache
Nov 1, 2011·Cell Communication and Signaling : CCS·Jens RauchWalter Kolch
Nov 10, 2004·The Journal of Cell Biology·Atsuo T SasakiRichard A Firtel
Jun 16, 2005·Annals of the New York Academy of Sciences·Carmen W Dessauer, Bao T Nguyen
Jan 25, 2005·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Erik Procko, Shaun R McColl
Jul 27, 2004·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Wouter H MoolenaarBen N G Giepmans
Jan 14, 2004·Journal of Thrombosis and Haemostasis : JTH·C SouletP Savi
Nov 20, 2003·Biological Psychiatry·Lara M TolbertRonald S Duman
Aug 5, 2015·Molecular and Cellular Endocrinology·Tali H Bar-LevZvi Naor
Jul 24, 2012·European Journal of Pharmacology·Aline Rosa NascimentoMaria Fatima Magalhaes Lazari
Dec 21, 2012·Journal of Receptor and Signal Transduction Research·Christine M LynchRonald W Matheny
Nov 1, 2002·Developmental Cell·Miho IijimaPeter Devreotes
Jul 25, 2003·The Journal of Biological Chemistry·Hicham LahlouChristiane Susini
Feb 25, 2005·American Journal of Physiology. Cell Physiology·C Chris YunHyunsuk Shim
Jan 3, 2019·Endocrinology·Anne R Bresnick, Jonathan M Backer
Aug 19, 2003·Nature Reviews. Molecular Cell Biology·Reinhard Wetzker, Frank-D Böhmer
Apr 5, 2008·The Journal of Pharmacology and Experimental Therapeutics·Mary P HornSusan A McDowell
Dec 28, 2002·The Journal of Biological Chemistry·Cornelia CzupallaBernd Nürnberg
Aug 11, 2005·The Biochemical Journal·Hiroshi KuboOsamu Hazeki
Oct 17, 2017·Journal of Immunoassay & Immunochemistry·Mahesh YanamandraSayan Mitra

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