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Allen JD , Jaffer ZM , Park SJ , Burgin S , Hofmann C , Sells MA , Chen S , Derr-Yellin E , Michels EG , McDaniel A , Bessler WK , Ingram DA , Atkinson SJ , Travers JB , Chernoff J , Clapp DW
p21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics
Blood. 2009 Mar;113(12) :2695-2705
PMID: 19124833    PMCID: PMC2661857    URL: https://www.ncbi.nlm.nih.gov/pubmed/19124833
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Mast cells are key participants in allergic diseases via activation of high-affinity IgE receptors (Fc epsilon RI) resulting in release of proinflammatory 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, W-sh/W-sh mast cell-deficient mice locally reconstituted with Pak1(-/-) bone marrow-derived mast cells (BMMCs) experienced strikingly decreased allergen-induced vascular permeability compared with controls. Consistent with the in vivo phenotype, Pak1(-/-) BMMCs exhibited a reduction in Fc epsilon RI-induced degranulation. Further, Pak1(-/-) BMMCs demonstrated diminished calcium mobilization and altered depolymerization of cortical filamentous actin (F-actin) in response to Fc epsilon RI stimulation. These data implicate Pak1 as an essential molecular target for modulating acute mast cell responses that contribute to allergic diseases. (Blood. 2009;113:2695-2705)
Allen, Jayme D. Jaffer, Zahara M. Park, Su-Jung Burgin, Sarah Hofmann, Clemens Sells, Mary Ann Chen, Shi Derr-Yellin, Ethel Michels, Elizabeth G. McDaniel, Andrew Bessler, Waylan K. Ingram, David A. Atkinson, Simon J. Travers, Jeffrey B. Chernoff, Jonathan Clapp, D. Wade AMER SOC HEMATOLOGY 421MA