The tyrosine kinase network regulating mast cell activation.

Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1930, USA.
Immunological Reviews (Impact Factor: 12.91). 04/2009; 228(1):149-69. DOI: 10.1111/j.1600-065X.2008.00742.x
Source: PubMed

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
    Biophysical Journal 01/2015; 108(2):99a. DOI:10.1016/j.bpj.2014.11.566 · 3.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Subsets of B cells inhibit various immune responses through their production of the cytokine interleukin-10 (IL-10). We found that IL-10-producing CD5(+) B cells suppressed the immunoglobulin E (IgE)- and antigen-mediated activation of mast cells in vitro as well as allergic responses in mice in an IL-10-dependent manner. Furthermore, the suppressive effect of these B cells on mast cells in vitro and in vivo depended on direct cell-to-cell contact through the costimulatory receptor CD40 on CD5(+) B cells and the CD40 ligand on mast cells. This contact enhanced the production of IL-10 by the CD5(+) B cells. Through activation of the Janus-activated kinase-signal transducer and activator of transcription 3 pathway, IL-10 decreased the abundance of the kinases Fyn and Fgr and inhibited the activation of the downstream kinase Syk in mast cells. Together, these findings suggest that an important function of IL-10-producing CD5(+) B cells is inhibiting mast cells and IgE-mediated allergic responses. Copyright © 2015, American Association for the Advancement of Science.
    Science Signaling 03/2015; 8(368):ra28. DOI:10.1126/scisignal.2005861 · 7.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Our long-term efforts to elucidate receptor-mediated signalling in immune cells, particularly transmembrane signalling initiated by FcɛRI, the receptor for IgE in mast cells, led us unavoidably to contemplate the role of the heterogeneous plasma membrane. Our early investigations with fluorescence microscopy revealed co-redistribution of certain lipids and signalling components with antigen-cross-linked IgE-FcɛRI and pointed to participation of ordered membrane domains in the signalling process. With a focus on this function, we have worked along with others to develop diverse and increasingly sophisticated tools to analyse the complexity of membrane structure that facilitates regulation and targeting of signalling events. The present chapter describes how initial membrane interactions of clustered IgE-FcɛRI lead to downstream cellular responses and how biochemical information integrated with nanoscale resolution spectroscopy and imaging is providing mechanistic insights at the level of molecular complexes.
    Essays in Biochemistry 02/2015; 57(1):147-163. DOI:10.1042/bse0570147 · 4.39 Impact Factor


Available from

Similar Publications