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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Abrams, C. S. Search for Related Content PubMed Articles by Abrams, C. S. Related Collections 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. 416-417 Collagen-mediated platelet activation and PI3K Phosphatidylinositol 3–kinase (PI3K) is a phospholipid kinase that is involved in diverse cellular events, including the prevention of apoptosis, regulation of glucose metabolism, chemotaxis, and cell proliferation. It is far from obvious what role this enzyme would play in a platelet—a terminally differentiated anucleate cell. Studies using less-than-specific pharmacologic inhibitors have a suggested that PI3K might participate in both collagen-induced platelet activation and the irreversible phase of platelet aggregation (Kovacsovics et al, J Biol Chem. 1995;270:11358-11366; Pasquet et al, Biochem J. 1999;342(pt 1): 171-177). Most cells have multiple isoforms of PI3K that are composed of a regulatory subunit and a catalytic subunit. Using cells obtained from genetically modified mice, investigators have begun to understand the role of different PI3K isoforms in hematopoietic cells. For example, mice lacking the p110 catalytic subunit of PI3K have a defect in ADP-mediated platelet aggregation (Hirsch et al, FASEB J. 2001;15:2019-2021), while mice lacking the p85 regulatory subunit of PI3K have impaired B-cell development. In this issue, Watanabe and colleagues (page 541) have studied the effects of the p85 knockout on platelet function. They found that in the absence of p85 there was a defect in signaling events initiated by the platelet collagen receptor, GPVI, whereas there was no defect in platelet activation following stimulation by other platelet agonists such as ADP or thrombin. It is noteworthy that GPVI signaling pathways are similar to those emanating from the B-cell antigen receptor, as well as other members of the immunoglobulin supergene family of receptors. Does the work by Watanabe et al suggest that therapeutic targeting of p85 would be a useful way to disrupt platelet activation following exposure to subendothelial collagen such as occurs during coronary plaque rupture? Given the ubiquitous expression and diverse functions of PI3K, such speculation is premature. Charles S. Abrams University of Pennsylvania CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: 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 Blood 2003 102: 541-548. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Abrams, C. S. Search for Related Content PubMed Articles by Abrams, C. S. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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