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Blood, 8 January 2009, Vol. 113, No. 2, pp. 447-457. Prepublished online as a Blood First Edition Paper on October 7, 2008; DOI 10.1182/blood-2008-06-162032. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-06-162032v1 113/2/447    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 Prévost, N. Articles by Shattil, S. J. Search for Related Content PubMed PubMed Citation Articles by Prévost, N. Articles by Shattil, S. J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Platelets and Thrombopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLATELETS AND THROMBOPOIESIS Group IVA cytosolic phospholipase A2 (cPLA2) and integrin IIbβ3 reinforce each other's functions during IIbβ3 signaling in platelets Nicolas Prévost1, John V. Mitsios1, Hisashi Kato1, John E. Burke2,3, Edward A. Dennis2,3, Takao Shimizu4, and Sanford J. Shattil1 Departments of 1 Medicine, 2 Chemistry and Biochemistry, and 3 Pharmacology, School of Medicine, University of California, San Diego, La Jolla; and 4 Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Tokyo, Tokyo, Japan Group IVA cytosolic phospholipase A2 (cPLA2) catalyzes release of arachidonic acid from glycerophospholipids, leading to thromboxane A2 (TxA2) production. Some platelet agonists stimulate cPLA2, but others require fibrinogen binding to IIbβ3 to elicit TxA2. Therefore, relationships between cPLA2 and IIbβ3 were examined. cPLA2 and a cPLA2 binding partner, vimentin, coimmunoprecipitated with IIbβ3 from platelets, independent of fibrinogen binding. Studies with purified proteins and with recombinant proteins expressed in CHO cells determined that the interaction between cPLA2 and IIbβ3 was indirect and was dependent on the IIb and β3 cytoplasmic tails. Fibrinogen binding to IIbβ3 caused an increase in integrin-associated cPLA2 activity in normal platelets, but not in cPLA2-deficient mouse platelets or in human platelets treated with pyrrophenone, a cPLA2 inhibitor. cPLA2 activation downstream of IIbβ3 had functional consequences for platelets in that it was required for fibrinogen-dependent recruitment of activated protein kinase Cβ to the IIbβ3 complex and for platelet spreading. Thus, cPLA2 and IIbβ3 interact to reinforce each other's functions during IIbβ3 signaling. This provides a plausible explanation for the role of IIbβ3 in TxA2 formation and in the defective hemostatic function of mouse or human platelets deficient in cPLA2. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Stefanini, R. C. Roden, and W. Bergmeier CalDAG-GEFI is at the nexus of calcium-dependent platelet activation Blood, September 17, 2009; 114(12): 2506 - 2514. [Abstract] [Full Text] [PDF]

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