Work

The tyrosine kinase network regulating mast cell activation

Year: 2009

Type: review

Abstract: 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 (Fc epsilon RI) 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 Fc epsilon RI and KIT to transmit downstream signaling events required for the regulation of mast cell activation. Whereas KIT possesses inherent tyrosine kinase activity, Fc epsilon RI 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 Fc epsilon RI-mediated mast cell activation.

Source: Immunological Reviews

DOI: 10.1111/j.1600-065x.2008.00742.x

Authors: Alasdair M. Gilfillan, Juan Rivera

Institutions: National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases

Language: English

Topic: Mast cells and histamine

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases

Awards: Molecular Regulation of Inflammation, Intracellular Signaling By The Cell Surface Receptor For IgE