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Blood, 19 March 2009, Vol. 113, No. 12, pp. 2695-2705. Prepublished online as a Blood First Edition Paper on January 5, 2009; DOI 10.1182/blood-2008-06-160861. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-06-160861v1 113/12/2695    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 Allen, J. D. Articles by Clapp, D. W. Search for Related Content PubMed PubMed Citation Articles by Allen, J. D. Articles by Clapp, D. W. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 3, 2008 Accepted December 9, 2008 P21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics Jayme D. Allen, Zahara M. Jaffer, Su-Jung Park, Sarah Burgin, Clemens Hofmann, Mary Ann Sells, Shi Chen, Ethel Derr-Yellin, Elizabeth G. Michels, Andrew McDaniel, Waylan K. Bessler, David A. Ingram, Simon J. Atkinson, Jeffrey B. Travers, Jonathan Chernoff, and D. Wade Clapp* Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, United States Department of Medicine, Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States Herman B Wells Center for Pediatric Research at Indiana University School of Medicine, Indianapolis, IN, United States Fox Chase Cancer Center, Philadelphia, PA, United States Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, United States * Corresponding author; email: dclapp{at}iupui.edu. Mast cells are key participants in allergic diseases via activation of high affinity IgE receptors (FcRI) resulting in release of pro-inflammatory mediators. The biochemical pathways linking IgE activation to calcium influx and cytoskeletal changes required for intracellular granule release are incompletely understood. We demonstrate, genetically, that Pak1 is required for this process. In a passive cutaneous anaphylaxis experiment, Wsh/Wsh mast cell-deficient mice locally reconstituted with Pak1-/- bone marrow-derived mast cells (BMMCs) experienced strikingly decreased allergen-induced vascular permeability as compared to controls. Consistent with the in vivo phenotype, Pak1-/- bone marrow-derived mast cells (BMMCs) exhibited a reduction in FcRI-induced degranulation. Further, Pak1-/- BMMCs demonstrated diminished calcium mobilization and altered depolymerization of cortical filamentous actin (F-actin) in response to FcRI stimulation. These data implicate Pak1 as an essential molecular target for modulating acute mast cell responses that contribute to allergic diseases CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Viaud and J. R. Peterson An allosteric kinase inhibitor binds the p21-activated kinase autoregulatory domain covalently Mol. Cancer Ther., September 1, 2009; 8(9): 2559 - 2565. [Abstract] [Full Text] [PDF] C. Van den Broeke, M. Radu, M. Deruelle, H. Nauwynck, C. Hofmann, Z. M. Jaffer, J. Chernoff, and H. W. Favoreel Alphaherpesvirus US3-mediated reorganization of the actin cytoskeleton is mediated by group A p21-activated kinases PNAS, May 26, 2009; 106(21): 8707 - 8712. [Abstract] [Full Text] [PDF]

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