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; D. Wade Clapp

doi:10.1182/blood-2008-06-160861

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, D. Wade Clapp

Research output: Contribution to journal › Article

86 Scopus citations

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 language	English (US)
Pages (from-to)	2695-2705
Number of pages	11
Journal	Blood
Volume	113
Issue number	12
DOIs	https://doi.org/10.1182/blood-2008-06-160861
State	Published - Mar 19 2009

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

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Allen, J. D., Jaffer, Z. M., Park, S. J., Burgin, S., Hofmann, C., Sells, M. A., Chen, S., Derr-Yellin, E., Michels, E. G., McDaniel, A., Bessler, W. K., Ingram, D. A., Atkinson, S. J., Travers, J. B., Chernoff, J., & Clapp, D. W. (2009). P21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics. Blood, 113(12), 2695-2705. https://doi.org/10.1182/blood-2008-06-160861

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 A.; Atkinson, Simon J.; Travers, Jeffrey B.; Chernoff, Jonathan; Clapp, D. Wade.

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

Research output: Contribution to journal › Article

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 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 A. ; Atkinson, Simon J. ; Travers, Jeffrey B. ; Chernoff, Jonathan ; Clapp, D. Wade. / 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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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.",

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AU - Hofmann, Clemens

AU - Sells, Mary Ann

AU - Chen, Shi

AU - Derr-Yellin, Ethel

AU - Michels, Elizabeth G.

AU - McDaniel, Andrew

AU - Bessler, Waylan K.

AU - Ingram, David A.

AU - Atkinson, Simon J.

AU - Travers, Jeffrey B.

AU - Chernoff, Jonathan

AU - Clapp, D. Wade

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