A novel integrin-activated pathway forms PKB/Akt-stimulatory phosphatidylinositol 3,4-bisphosphate via phosphatidylinositol 3-phosphate in platelets.

The Journal of Biological Chemistry
H BanfićS E Rittenhouse

Abstract

The aggregation of human platelets is an important physiological hemostatic event contingent upon receptor-dependent activation of the surface integrin alphaIIbbeta3 and subsequent binding of fibrinogen. Aggregating platelets form phosphatidylinositol 3, 4-bisphosphate (PtdIns(3,4)P2), which has been reported to stimulate in vitro the activity of the proto-oncogenic protein kinase PKB/Akt, as has phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). It has been assumed that PtdIns(3,4)P2 is synthesized by either 5-phosphatase-catalyzed hydrolysis of PtdIns(3,4,5)P3 produced by phosphoinositide 3-kinase (PI3K) or phosphorylation by PI3K of PtdIns4P. We investigated the route(s) by which PtdIns(3,4)P2 is formed after directly activating alphaIIbbeta3 with anti-ligand-induced binding site Fab fragment and report that aggregation does not lead to the generation of PtdIns(3,4,5)P3, but to transient formation of PtdIns3P and generation of PtdIns(3,4)P2, the latter primarily by PtdIns3P 4-kinase. Both this novel pathway and the activation of PKB/Akt are inhibited by the PI3K inhibitor, wortmannin, and the calpain inhibitor, calpeptin, constituting the first evidence that PtdIns(3,4)P2 can stimulate PKB/Akt in vivo in the absence...Continue Reading

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Citations

Sep 6, 2002·Journal of Peptide Science : an Official Publication of the European Peptide Society·Dirk WeberHorst Kessler
Apr 3, 2012·Journal of Molecular Neuroscience : MN·Shiv S PrasadCarole Yauk
Jun 8, 1999·Chemistry and Physics of Lipids·K F Tolias, L C Cantley
Sep 7, 2001·Current Opinion in Cell Biology·D R PhillipsL Nannizzi-Alaimo
Mar 3, 1999·The Biochemical Journal·S SarkarS T Lord
Aug 6, 2000·The Biochemical Journal·M A Lemmon, K M Ferguson
Apr 4, 2001·The Biochemical Journal·D J GilloolyH Stenmark
Aug 8, 2002·Clinical and Experimental Pharmacology & Physiology·Joseph I Kourie, Christine L Henry
Oct 1, 2003·Clinical and Experimental Pharmacology & Physiology·Angela F Dulhunty, Pierre Pouliquin
Mar 1, 2003·Pathology International·Munehiko OndaYuichi Sugisaki
Mar 20, 2003·Journal of Cardiac Surgery·Valeri S ChekanovMasood Akhtar
Jan 26, 2011·Molecular & Cellular Proteomics : MCP·Miles J DixonIan H Batty
Nov 29, 2008·Cardiovascular Research·Fulvio MorelloEmilio Hirsch
Oct 6, 1998·Annual Review of Biochemistry·D A FrumanL C Cantley
Jun 8, 2001·Annual Review of Biochemistry·B VanhaesebroeckM D Waterfield
Apr 23, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Jen-Hwey Chiu
Feb 3, 2004·The Journal of Clinical Investigation·Donna WoulfeLawrence F Brass
Aug 9, 2011·Blood·Kelly A O'BrienXiaoping Du
Nov 2, 2001·Biochemical and Biophysical Research Communications·F PaulheC Racaud-Sultan
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·A D MundayC A Mitchell
Mar 4, 2000·The Biochemical Journal·B Vanhaesebroeck, D R Alessi
Jan 5, 2002·Expert Opinion on Investigational Drugs·C P Berrie
Jun 28, 2014·Journal of Neuroimmunology·Lindsay J SpielmanAndis Klegeris
Jun 24, 2003·The American Journal of Pathology·Jonas M la CourMartin W Berchtold
May 25, 2005·Pediatrics International : Official Journal of the Japan Pediatric Society·Fangqi GongManli Kang
Apr 16, 2003·Traffic·Mark A Lemmon
Jul 1, 2010·Journal of Thrombosis and Haemostasis : JTH·B XiangZ Li
Feb 10, 2012·Journal of Veterinary Emergency and Critical Care·Robert Goggs, Alastair W Poole
Jul 19, 2005·Advances in Enzyme Regulation·Caroline PendariesBernard Payrastre

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