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Blood, 1 July 2005, Vol. 106, No. 1, pp. 110-117. Prepublished online as a Blood First Edition Paper on February 10, 2005; DOI 10.1182/blood-2004-05-2005. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-05-2005v1 106/1/110    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lian, L. Articles by Abrams, C. S. Search for Related Content PubMed PubMed Citation Articles by Lian, L. Articles by Abrams, C. S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The relative role of PLC and PI3K in platelet activation Lurong Lian, Yanfeng Wang, Julia Draznin, Don Eslin, Joel S. Bennett, Mortimer Poncz, Dianqing Wu, and Charles S. Abrams From the Department of Medicine of the University of Pennsylvania, Philadelphia; Children's Hospital of Philadelphia, PA; and the Department of Genetics & Developmental Biology, University of Connecticut Health Center, Farmington. Stimulation of platelet G protein–coupled receptors results in the cleavage of phosphatidylinositol 4,5-trisphosphate (PIP2) into inositol 1,4,5-trisphosphate and 1,2-diacylglycerol by phospholipase C (PLC). It also results in the phosphorylation of PIP2 by the isoform of phosphatidylinositol 3-kinase (PI3K) to synthesize phosphatidylinositol 3,4,5-trisphosphate. To understand the role of PIP2 in platelet signaling, we evaluated knock-out mice lacking 2 isoforms of PLC (PLC2 and PLC3) or lacking the G-activated isoform of PI3K (PI3K). Both knock-out mice were unable to form stable thrombi in a carotid injury model. To provide a functional explanation, knock-out platelets were studied ex vivo. PLC2/3–/– platelets failed to assemble filamentous actin, had defects in both secretion and mobilization of intracellular calcium, and were unable to form stable aggregates following low doses of agonists. Platelets lacking PI3K disaggregated following low-dose adenosine diphosphate (ADP) and had a mildly impaired ability to mobilize intracellular calcium. Yet, they exhibited essentially normal actin assembly and secretion. Remarkably, both PLC2/3–/– and PI3K–/– platelets spread more slowly upon fibrinogen. These results suggest substantial redundancy in platelet signaling pathways. Nonetheless, the diminished ability of knock-out platelets to normally spread after adhesion and to form stable thrombi in vivo suggests that both PLC2/3 and PI3K play vital roles in platelet cytoskeletal dynamics. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Morello, A. Perino, and E. Hirsch Phosphoinositide 3-kinase signalling in the vascular system Cardiovasc Res, May 1, 2009; 82(2): 261 - 271. [Abstract] [Full Text] [PDF] L. Lian, Y. Wang, M. Flick, J. Choi, E. W. Scott, J. Degen, M. A. Lemmon, and C. S. Abrams Loss of pleckstrin defines a novel pathway for PKC-mediated exocytosis Blood, April 9, 2009; 113(15): 3577 - 3584. [Abstract] [Full Text] [PDF] M. Grenegard, K. Vretenbrant-Oberg, M. Nylander, S. Desilets, E. G. Lindstrom, A. 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