A BASH/SLP-76-related adaptor protein MIST/Clnk involved in IgE receptor-mediated mast cell degranulation.
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.
Goitsuka
R
R
Division of Molecular Biology, Research Institute for Biological Sciences, Science University of Tokyo, 2669 Yamazaki, Noda, Chiba 278, Japan.
Kanazashi
H
H
Sasanuma
H
H
Fujimura
Y
Y
Hidaka
Y
Y
Tatsuno
A
A
Ra
C
C
Hayashi
K
K
Kitamura
D
D
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*
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