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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2002-11-3327. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-11-3327v1 102/2/541    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 Watanabe, N. Articles by Handa, M. Search for Related Content PubMed PubMed Citation Articles by Watanabe, N. Articles by Handa, M. Related Collections Cell Adhesion and Motility Signal Transduction Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 July 2003, Vol. 102, No. 2, pp. 541-548 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Functional phenotype of phosphoinositide 3-kinase p85-null platelets characterized by an impaired response to GP VI stimulation Naohide Watanabe, Hideaki Nakajima, Hidenori Suzuki, Atsushi Oda, Yumiko Matsubara, Masaaki Moroi, Yasuo Terauchi, Takashi Kadowaki, Harumi Suzuki, Shigeo Koyasu, Yasuo Ikeda, and Makoto Handa From the Blood Center, Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo; the Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo; the Division of Cellular Therapy, Institute of Medical Science, University of Tokyo; the Department of Cardiovascular Research, Tokyo Metropolitan Institute of Medical Science; the Laboratory of Environmental Biology, Department of Preventive Medicine, Hokkaido University School of Medicine, Sapporo; the Institute of Life Science, Kurume University; the Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo; Core Research for Evolutional Science and Technology Corporation, Kawaguchi; and the Department of Microbiology and Immunology, Yamaguchi University School of Medicine, Ube, Japan. Phosphoinositide 3-kinases (PI3Ks), a family of lipid kinases comprising 3 classes with multiple isoforms, have been shown to participate in different phases of platelet signaling. To investigate the roles that enzymes play in platelet function in vivo and determine which isoforms are important for particular signaling events, we analyzed platelet function of gene knockout mice deficient in the p85 regulatory subunit of heterodimeric class IA PI3K. The kinase activity of p85—/— platelets was only 5% of the activity of platelets from wild-type littermates. Platelet aggregation induced by adenosine diphosphate (ADP), thrombin, U46619, phorbol 12-myristate 13-acetate (PMA), or botrocetin was not defective in p85—/— mice, compared with wild-type animals. In contrast, aggregation induced by collagen and collagen-related peptide (CRP) was partially but readily impaired in p85—/— mice. Both P-selectin expression and fibrinogen binding in response to CRP were also decreased to a similar extent in p85—/— platelets. Platelets from p85—/— mice appeared to spread poorly over a CRP-coated surface with intact filopodial protrusions. Significant attenuation of CRP-induced tyrosine phosphorylation in known PI3K effectors such as Btk, Tec, PKB/Akt, and phospholipase C2 were observed with p85—/— platelets, whereas no alteration was noted in upstream molecules of Syk, LAT, and SLP-76. Considered as a whole, these results provide the first genetic evidence that PI3K p85 plays a significant role in platelet function, almost exclusively in the glycoprotein (GP) VI/Fc receptor chain complex-mediated signaling pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Collagen-mediated platelet activation and PI3K Charles S. Abrams Blood 2003 102: 416-417. 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