title: A BASH/SLP-76-related adaptor protein MIST/Clnk involved in IgE receptor-mediated mast cell degranulation.
abstract: Cross-linking of the high-affinity IgE receptor (FcepsilonRI) 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 FcepsilonRI cross-linking, MIST/Clnk is tyrosine phosphorylated and associates with signaling proteins, phospholipase Cgamma, Vav, Grb2 and linker for activation of T cells (LAT). Overexpression of a mutant form of MIST/Clnk inhibited FcepsilonRI-mediated degranulation, increase in intracellular Ca(2+), NF-AT activation and phosphorylation of LAT. As a crucial signaling component for FcepsilonRI-induced mast cell degranulation, MIST/Clnk might serve as a target for anti-allergic therapy.
authors.affiliation: Division of Molecular Biology, Research Institute for Biological Sciences, Science University of Tokyo, 2669 Yamazaki, Noda, Chiba 278, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Goitsuka
authors.forename: H
authors.initials: H
authors.lastname: Kanazashi
authors.forename: H
authors.initials: H
authors.lastname: Sasanuma
authors.forename: Y
authors.initials: Y
authors.lastname: Fujimura
authors.forename: Y
authors.initials: Y
authors.lastname: Hidaka
authors.forename: A
authors.initials: A
authors.lastname: Tatsuno
authors.forename: C
authors.initials: C
authors.lastname: Ra
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: D
authors.initials: D
authors.lastname: Kitamura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D015550:Cell Degranulation / Q000276:immunology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000737:chemistry*; D017455:Receptors, IgE / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; C411024:CLNK protein, human; D002352:Carrier Proteins; D010750:Phosphoproteins; D017455:Receptors, IgE; C092947:SLP-76 signal Transducing adaptor proteins