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Prepublished online as a Blood First Edition Paper on October 10, 2002; DOI 10.1182/blood-2002-08-2384. This Article Full Text (PDF) All Versions of this Article: 2002-08-2384v1 101/4/1392    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 Citing Articles via Google Scholar Google Scholar Articles by Stafford, M. J Articles by Pears, C. J Search for Related Content PubMed PubMed Citation Articles by Stafford, M. J Articles by Pears, C. J Social Bookmarking                   What's this? Submitted August 7, 2002 Accepted September 25, 2002 PKD: A new protein kinase C dependent pathway in platelets Margaret J Stafford*, Steve P Watson, and Catherine J Pears Department of Biochemistry, Oxford University, Oxford, United Kingdom Department of Pharmacology, Oxford University, Oxford, United Kingdom * Corresponding author; email: margaret{at}bioch.ox.ac.uk. Protein kinase D (PKD; also known as PKCµ) is closely related to the protein kinase C superfamily but is differentially regulated and has a distinct catalytic domain which shares homology with Ca2+-dependent protein kinases. PKD is highly expressed in haematopoietic cells and undergoes rapid and sustained activation upon stimulation of immune receptors. PKD is regulated through phosphorylation by protein kinase C (PKC). In the present study, we show that PKD is expressed in human platelets and that it is rapidly activated by receptors coupled to heterotrimeric G-proteins or tyrosine kinases. Activation of PKD is mediated downstream of PKC. Strong agonists such as convulxin, which acts on GPVI, and thrombin cause sustained activation of PKC and PKD, whereas the thromboxane mimetic U46619 gives rise to transient activation of PKC and PKD. Activation of PKD by submaximal concentrations of phospholipase C-coupled receptor agonists is potentiated by Gi-coupled receptors e.g. ADP and epinephrine. This study shows that PKD is rapidly activated by a wide variety of platelet agonists through a PKC-dependent pathway. Activation of PKD enables phosphorylation of a distinct set of substrates to those targetted by PKC in platelets. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Avkiran, A. J. Rowland, F. Cuello, and R. S. Haworth Protein Kinase D in the Cardiovascular System: Emerging Roles in Health and Disease Circ. Res., February 1, 2008; 102(2): 157 - 163. [Abstract] [Full Text] [PDF] M. Hoffmeister, P. Riha, O. Neumuller, O. Danielewski, J. Schultess, and A. P. Smolenski Cyclic Nucleotide-dependent Protein Kinases Inhibit Binding of 14-3-3 to the GTPase-activating Protein Rap1GAP2 in Platelets J. Biol. Chem., January 25, 2008; 283(4): 2297 - 2306. [Abstract] [Full Text] [PDF] E. Rozengurt, O. Rey, and R. T. Waldron Protein Kinase D Signaling J. Biol. Chem., April 8, 2005; 280(14): 13205 - 13208. [Full Text] [PDF] C. S. Buensuceso, A. Obergfell, A. Soriani, K. Eto, W. B. Kiosses, E. G. Arias-Salgado, T. Kawakami, and S. J. Shattil Regulation of Outside-in Signaling in Platelets by Integrin-associated Protein Kinase C{beta} J. Biol. Chem., January 7, 2005; 280(1): 644 - 653. [Abstract] [Full Text] [PDF]

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