A BASH/SLP-76-related adaptor protein MIST/CInk involved in IgE receptor-mediated mast cell degranulation
A BASH/SLP-76-related adaptor protein MIST/CInk involved in IgE receptor-mediated mast cell degranulation
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DOI：
10.1093/intimm/12.4.573
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发表时间：
2000-04-01
影响因子：
4.4
通讯作者：
Kitamura, D
中科院分区：
文献类型：
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作者：
Goitsuka, R;Kanazashi, H;Kitamura, D
通过IgE-抗原复合物交联肥大细胞上的高亲和力IgE受体（Fc ε RI）触发信号转导级联，导致炎症介质的释放和细胞因子的产生，这对于过敏反应的发展至关重要。我们已经确定了一个新的成员的BASH/SLP-76免疫受体偶联衔接家庭表达的肥大细胞，称为MIST（用于肥大细胞免疫受体信号转导子），后来发现其与最近报道的依赖于精氨酸的造血细胞连接子Cink相同。在Fc γ RI交联后，MIST/Cink被酪氨酸磷酸化并与信号蛋白磷脂酶C γ，Vav，突变型MIST/Clnk的过表达可抑制Fc γ RI介导的肥大细胞脱颗粒，增加细胞内Ca ~（2+）、NF-AT的活化和LAT的磷酸化。MIST/Clnk作为Fc γ RI诱导的肥大细胞脱颗粒的重要信号成分，可能成为抗过敏治疗的靶点。
Cross-linking of the high-affinity IgE receptor (Fc epsilon RI) 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, Cink, Upon Fc epsilon RI cross-linking, MIST/Clnk is tyrosine phosphorylated and associates with signaling proteins, phospholipase C gamma, Vav, Grb2 and linker for activation of T cells (LAI), Overexpression of a mutant form of MIST/Clnk inhibited Fc epsilon RI-mediated degranulation, increase in intracellular Ca2+, NF-AT activation and phosphorylation of LAT, As a crucial signaling component for Fc epsilon RI-induced mast cell degranulation, MIST/Clnk might serve as a target for anti-allergic therapy.