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Blood, 15 July 2005, Vol. 106, No. 2, pp. 550-557. Prepublished online as a Blood First Edition Paper on April 5, 2005; DOI 10.1182/blood-2004-12-4866. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-12-4866v1 106/2/550    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 Murugappan, S. Articles by Kunapuli, S. P. Search for Related Content PubMed PubMed Citation Articles by Murugappan, S. Articles by Kunapuli, S. P. 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 Molecular mechanism and functional implications of thrombin-mediated tyrosine phosphorylation of PKC in platelets Swaminathan Murugappan, Haripriya Shankar, Surya Bhamidipati, Robert T. Dorsam, Jianguo Jin, and Satya P. Kunapuli From the Department of Physiology, Temple University School of Medicine, Philadelphia, PA; the Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA; and the Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA. Thrombin has been known to cause tyrosine phosphorylation of protein kinase C (PKC) in platelets, but the molecular mechanisms and function of this tyrosine phosphorylation is not known. In this study, we investigated the signaling pathways used by protease-activated receptors (PARs) to cause tyrosine phosphorylation of PKC and the role of this event in platelet function. PKC was tyrosine phosphorylated by either PAR1 or PAR4 in a concentration- and time-dependent manner in human platelets. In particular, the tyrosine 311 residue was phosphorylated downstream of PAR receptors. Also the tyrosine phosphorylation of PKC did not occur in Gq-deficient mouse platelets and was inhibited in the presence of a phospholipase C (PLC) inhibitor U73122 and calcium chelator BAPTA (5,5'-dimethyl-bis(o-aminophenoxy)ethane-N, N, N ', N '-tetraacetic acid), suggesting a role for Gq pathways and calcium in this event. Both PAR1 and PAR4 caused a time-dependent activation of Src (pp60c-src) tyrosine kinase and Src tyrosine kinase inhibitors completely blocked the tyrosine phosphorylation of PKC. Inhibition of tyrosine phosphorylation or the kinase activity of PKC dramatically blocked PAR-mediated thromboxane A2 generation. We conclude that thrombin causes tyrosine phosphorylation of PKC in a calcium- and Src-family kinase–dependent manner in platelets, with functional implications in thromboxane A2 generation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Chari, T. Getz, B. Nagy Jr, K. Bhavaraju, Y. Mao, Y. S. Bynagari, S. Murugappan, K. Nakayama, and S. P. Kunapuli Protein Kinase C{delta} Differentially Regulates Platelet Functional Responses Arterioscler Thromb Vasc Biol, May 1, 2009; 29(5): 699 - 705. [Abstract] [Full Text] [PDF] B. Nagy Jr, K. Bhavaraju, T. Getz, Y. S. Bynagari, S. Kim, and S. P. Kunapuli Impaired activation of platelets lacking protein kinase C-{theta} isoform Blood, March 12, 2009; 113(11): 2557 - 2567. [Abstract] [Full Text] [PDF] Z. A. Karim, W. Choi, and S. W. 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