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 Ingram, Simon J. Atkinson, Jeffrey Travers, Jonathan Chernoff, D. Clapp

Research output: Contribution to journalArticle

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Abstract

Mast cells are key participants in allergic diseases via activation of high-affinity IgE receptors (FcεRI) 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 FcεRI-induced degranulation. Further, Pak1 -/- BMMCs demonstrated diminished calcium mobilization and altered depolymerization of cortical filamentous actin (F-actin) in response to FcεRI stimulation. These data implicate Pak1 as an essential molecular target for modulating acute mast cell responses that contribute to allergic diseases.

Original languageEnglish
Pages (from-to)2695-2705
Number of pages11
JournalBlood
Volume113
Issue number12
DOIs
StatePublished - Mar 19 2009

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p21-Activated Kinases
Cell Degranulation
Mast Cells
Bone
Calcium
Chemical activation
IgE Receptors
Depolymerization
Bone Marrow
Allergens
Immunoglobulin E
Actins
Passive Cutaneous Anaphylaxis
Capillary Permeability
Experiments
Phenotype

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

P21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics. / 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; Atkinson, Simon J.; Travers, Jeffrey; Chernoff, Jonathan; Clapp, D.

In: Blood, Vol. 113, No. 12, 19.03.2009, p. 2695-2705.

Research output: Contribution to journalArticle

Allen, JD, Jaffer, ZM, Park, SJ, Burgin, S, Hofmann, C, Sells, MA, Chen, S, Derr-Yellin, E, Michels, EG, McDaniel, A, Bessler, WK, Ingram, D, Atkinson, SJ, Travers, J, Chernoff, J & Clapp, D 2009, 'P21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics', Blood, vol. 113, no. 12, pp. 2695-2705. https://doi.org/10.1182/blood-2008-06-160861
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 ; Atkinson, Simon J. ; Travers, Jeffrey ; Chernoff, Jonathan ; Clapp, D. / P21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics. In: Blood. 2009 ; Vol. 113, No. 12. pp. 2695-2705.
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