p21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics

被引：90

作者：

Allen, Jayme D. ^{[2
]}

Jaffer, Zahara M. ^{[3
]}

Park, Su-Jung ^{[2
]}

Burgin, Sarah ^{[2
]}

Hofmann, Clemens ^{[4
]}

Sells, Mary Ann ^{[4
]}

Chen, Shi ^{[2
]}

Derr-Yellin, Ethel ^{[2
]}

Michels, Elizabeth G. ^{[2
]}

McDaniel, Andrew ^{[6
]}

Bessler, Waylan K. ^{[2
]}

Ingram, David A. ^{[2
]}

Atkinson, Simon J. ^{[3
]}

Travers, Jeffrey B. ^{[2
,5
]}

Chernoff, Jonathan ^{[4
]}

Clapp, D. Wade ^{[1
,2
,6
]}

机构：

[1] Indiana Univ, Sch Med, Herman B Wells Ctr Pediat Res, Canc Res Inst, Indianapolis, IN 46202 USA

[2] Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA

[3] Indiana Univ, Sch Med, Dept Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA

[4] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA

[5] Indiana Univ, Sch Med, Dept Dermatol, Indianapolis, IN USA

[6] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN USA

来源：

BLOOD | 2009年 / 113卷 / 12期

基金：

美国国家卫生研究院;

关键词：

FC-EPSILON-RI; IN-VIVO; ACTIVATION; MICROTUBULE; PAK1; CHANNELS; RECEPTOR; PHOSPHORYLATION; TRANSLOCATION; LYMPHOCYTES;

D O I：

10.1182/blood-2008-06-160861

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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)

引用

页码：2695 / 2705

页数：11

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