Cross-linking of the high-affinity IgE receptor (FcεRI) on mast cells by IgE-antigen complex triggers signal transduction cascades leading to the release of inflammatory mediators and production of cytokines, which are critical for the development of allergic reactions. We have identified a novel member of the BASH/SLP-76 immunoreceptor-coupled adaptor family expressed in mast cells, termed MIST (for mast cell immunoreceptor signal transducer), which has later been found to be identical to a recently reported cytokine-dependent hemopoietic cell linker, Clnk. Upon FcεRI cross-linking, MIST/Clnk is tyrosine phosphorylated and associates with signaling proteins, phospholipase Cγ, Vav, Grb2 and linker for activation of T cells (LAT). Overexpression of a mutant form of MIST/Clnk inhibited FcεRI-mediated degranulation, increase in intracellular Ca2+, NF-AT activation and phosphorylation of LAT. As a crucial signaling component for FcεRI-induced mast cell degranulation, MIST/Clnk might serve as a target for anti-allergic therapy.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy