A BASH/SLP-76-related adaptor protein MIST/Clnk involved in IgE receptor-mediated mast cell degranulation

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Abstract
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.