Abstract
Mast cells function as the initiator of the allergic reaction and play a role in the innate immune system. Aggregation of the high affinity IgE receptor (FcεRI) on mast cells triggers degranulation with the release of chemical mediators such as histamine, production of cytokines and leukotrienes. FcεRI signals by activating proximal non-receptor type of protein-tyrosine kinases, Lyn, Syk, Btk and Fyn. Activated tyrosine kinases then phosphorylate their specific substrates which include other enzymes and adaptor proteins and assemble these cytoplasmic signaling molecules for cellular activation. The adaptor proteins have multiple domains that allow binding to effector molecules and therefore act as positive or negative regulators controlling FcεRI signaling. Deletion of the adaptor proteins such as LAT, SLP-76 or Gab2 resulted in decreased FcεRI-mediated anaphylactic reaction in vivo. Functional analysis of adaptor proteins has raised the possibility that they may be new targets for the discovery of anti-allergic drugs.
Keywords: protein tyrosine kinases, adaptor protein, mediated, mast cells, ige receptor, lyn, src family
Current Molecular Medicine
Title: Protein-Tyrosine Kinases and Adaptor Proteins in FcεRI-Mediated Signaling in Mast Cells
Volume: 3 Issue: 1
Author(s): Kiyonao Sada and Hirohei Yamamura
Affiliation:
Keywords: protein tyrosine kinases, adaptor protein, mediated, mast cells, ige receptor, lyn, src family
Abstract: Mast cells function as the initiator of the allergic reaction and play a role in the innate immune system. Aggregation of the high affinity IgE receptor (FcεRI) on mast cells triggers degranulation with the release of chemical mediators such as histamine, production of cytokines and leukotrienes. FcεRI signals by activating proximal non-receptor type of protein-tyrosine kinases, Lyn, Syk, Btk and Fyn. Activated tyrosine kinases then phosphorylate their specific substrates which include other enzymes and adaptor proteins and assemble these cytoplasmic signaling molecules for cellular activation. The adaptor proteins have multiple domains that allow binding to effector molecules and therefore act as positive or negative regulators controlling FcεRI signaling. Deletion of the adaptor proteins such as LAT, SLP-76 or Gab2 resulted in decreased FcεRI-mediated anaphylactic reaction in vivo. Functional analysis of adaptor proteins has raised the possibility that they may be new targets for the discovery of anti-allergic drugs.
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Cite this article as:
Sada Kiyonao and Yamamura Hirohei, Protein-Tyrosine Kinases and Adaptor Proteins in FcεRI-Mediated Signaling in Mast Cells, Current Molecular Medicine 2003; 3 (1) . https://dx.doi.org/10.2174/1566524033361618
DOI https://dx.doi.org/10.2174/1566524033361618 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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