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Blood, 1 October 2009, Vol. 114, No. 14, pp. 3056-3063. Prepublished online as a Blood First Edition Paper on July 8, 2009; DOI 10.1182/blood-2008-11-188516. This Article Full Text (PDF) All Versions of this Article: blood-2008-11-188516v1 114/14/3056    most recent 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 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 Google Scholar Articles by Chari, R. Articles by Kunapuli, S. P. PubMed PubMed Citation Articles by Chari, R. Articles by Kunapuli, S. P. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 7, 2008 Accepted May 14, 2009 Lyn, PKC delta, SHIP-1 interactions regulate GPVI-mediated platelet dense granule secretion Ramya Chari, Soochong Kim, Swaminathan Murugappan, Archana Sanjay, James L. Daniel, and Satya P. Kunapuli* Department of Physiology, Temple University School of Medicine, Philadelphia, PA, United States Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, United States Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA, United States Pharmacology, Temple University School of Medicine, Philadelphia, PA, United States * Corresponding author; email: spk{at}temple.edu. Protein Kinase C (PKC) is expressed in platelets and activated downstream of protease-activated receptors (PAR)s and Glycoprotein VI (GPVI) receptors. We have previously shown that PKC positively regulates PAR-mediated dense granule secretion, whereas it negatively regulates GPVI-mediated dense granule secretion. We further investigated the mechanism of such differential regulation of dense granule release by PKC in platelets. SH2 domain-containing Inositol Phosphatase (SHIP)-1 is phosphorylated on Y1020, a marker for its activation, upon stimulation of human platelets with PAR agonists, SFLLRN and AYPGKF, or GPVI agonist, convulxin. GPVI-mediated SHIP-1 phosphorylation occurred rapidly at 15 sec whereas PAR-mediated phosphorylation was delayed, occurring at 1 min. Lyn and SHIP-1, but not SHIP-2 or Shc, preferentially associated with PKC upon stimulation of platelets with a GPVI agonists, but not with a PAR agonist. In PKC null murine platelets, convulxin-induced SHIP-1 phosphorylation was inhibited. Furthermore, in Lyn null murine platelets, GPVI-mediated phosphorylations on Y1020 of SHIP-1 and Y311 of PKC were inhibited. In murine platelets lacking Lyn, or SHIP-1, GPVI-mediated dense granule secretions are potentiated, whereas PAR-mediated dense granule secretions are inhibited. Therefore, we conclude that Lyn-mediated phosphorylations of PKC and SHIP-1 and their associations negatively regulate GPVI-mediated dense granule secretion in platelets. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Lyn and PKC order SHIP1 embargo Ulhas P. Naik Blood 2009 114: 2856-2857. [Full Text] [PDF] This article has been cited by other articles: U. P. Naik Lyn and PKC{delta} order SHIP1 embargo Blood, October 1, 2009; 114(14): 2856 - 2857. [Full Text] [PDF]

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