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The tyrosine kinase network regulating mast cell activation

Authors

  • Alasdair M. Gilfillan,

    1. Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
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  • Juan Rivera

    1. Laboratory of Immune Cell Signaling, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
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Juan Rivera
Laboratory of Immune Cell Signaling
NIAMS, NIH
Building 10, Room 13C103
MSC1930
10 Center Drive
Bethesda, MD 20892-1930, USA
Tel.: +1 301 496 7592
Fax: +1 301 480 1580
e-mail: juan-rivera@nih.gov

Abstract

Summary:  Mast cell mediator release represents a pivotal event in the initiation of inflammatory reactions associated with allergic disorders. These responses follow antigen-mediated aggregation of immunoglobulin E (IgE)-occupied high-affinity receptors for IgE (FcεRI) on the mast cell surface, a response which can be further enhanced following stem cell factor-induced ligation of the mast cell growth factor receptor KIT (CD117). Activation of tyrosine kinases is central to the ability of both FcεRI and KIT to transmit downstream signaling events required for the regulation of mast cell activation. Whereas KIT possesses inherent tyrosine kinase activity, FcεRI requires the recruitment of Src family tyrosine kinases and Syk to control the early receptor-proximal signaling events. The signaling pathways propagated by these tyrosine kinases can be further upregulated by the Tec kinase Bruton’s tyrosine kinase and downregulated by the actions of the tyrosine Src homology 2 domain-containing phosphatase 1 (SHP-1) and SHP-2. In this review, we discuss the regulation and role of specific members of this tyrosine kinase network in KIT and FcεRI-mediated mast cell activation.

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