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Blood, 9 April 2009, Vol. 113, No. 15, pp. 3577-3584. Prepublished online as a Blood First Edition Paper on February 3, 2009; DOI 10.1182/blood-2008-09-178913. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-09-178913v1 113/15/3577    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lian, L. Articles by Abrams, C. S. Search for Related Content PubMed PubMed Citation Articles by Lian, L. Articles by Abrams, C. S. Related Collections Platelets and Thrombopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLATELETS AND THROMBOPOIESIS Loss of pleckstrin defines a novel pathway for PKC-mediated exocytosis Lurong Lian1,*, Yanfeng Wang1,*, Matthew Flick2, John Choi3, Edward W. Scott4, Jay Degen2, Mark A. Lemmon5, and Charles S. Abrams1 1 Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia; 2 University of Cincinnati College of Medicine, OH; 3 Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia; 4 University of Florida Health Science Center, Gainesville; and 5 Department of Biochemistry and Molecular Biophysics, University of Pennsylvania School of Medicine, Philadelphia Pleckstrin, the platelet and leukocyte C kinase substrate, is a prominent substrate of PKC in platelets, monocytes, macrophages, lymphocytes, and granulocytes. Pleckstrin accounts for 1% of the total protein in these cells, but it is best known for containing the 2 prototypic Pleckstrin homology, or PH, domains. Overexpressed pleckstrin can affect polyphosphoinositide second messenger–based signaling events; however, its true in vivo role has been unknown. Here, we describe mice containing a null mutation within the pleckstrin gene. Platelets lacking pleckstrin exhibit a marked defect in exocytosis of and granules, IIbβ3 activation, actin assembly, and aggregation after exposure to the PKC stimulant, PMA. Pleckstrin-null platelets aggregate normally in response to thrombin, but they fail to aggregate in response to thrombin in the presence of PI3K inhibitors, suggesting that a PI3K-dependent signaling pathway compensates for the loss of pleckstrin. Although pleckstrin-null platelets merged their granules in response to stimulation of PKC, they failed to empty their contents into the open canalicular system. This might be attributable to impaired actin assembly present in cells lacking pleckstrin. These data show that pleckstrin regulates the fusion of granules to the cell membrane and is an essential component of PKC-mediated exocytosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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