LAT is essential for FcεRI-mediated mast cell activation
LAT is essential for FcεRI-mediated mast cell activation
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DOI：
10.1016/s1074-7613(00)80204-6
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发表时间：
2000-05-01
期刊：
影响因子：
32.4
通讯作者：
Samelson, LE
中科院分区：
文献类型：
--
作者：
Saitoh, S;Arudchandran, R;Samelson, LE
连接分子LAT是酪氨酸激酶的底物，在TCR与T细胞结合后被激活。LAT也在血小板、NK细胞和肥大细胞中表达。虽然lat缺陷小鼠含有正常数量的肥大细胞，但我们发现lat缺陷小鼠对ige介导的被动全身过敏反应具有抗性。缺乏lata的骨髓来源肥大细胞（BMMC）生长发育正常。然而，在与Fc ε - RI结合后，在latc缺失的bmmc中，Fc ε - on RI、Syk和Vav的酪氨酸磷酸化是完整的，而SLP-76、PLC-gamma 1和PLC-gamma 2的酪氨酸磷酸化和钙动员则显著减少。在Fc epsilon RI交联后，缺乏lata的bmmc在MAPK激活、脱颗粒和细胞因子产生方面也表现出严重缺陷。这些结果表明，LAT在肥大细胞中Fc epsilon i介导的信号传导中起着关键作用。
The linker molecule LAT is a substrate of the tyrosine kinases activated following TCR engagement of T cells. LAT is also expressed in platelets, NK, and mast cells. Although LAT-deficient mice contain normal numbers of mast cells, we found that LAT-deficient mice were resistant to IgE-mediated passive systemic anaphylaxis. LAT-deficient bone marrow-derived mast cells (BMMC) showed normal growth and development. Whereas tyrosine phosphorylation of Fc epsilon RI, Syk, and Vav was intact in LAT-deficient BMMCs following Fc epsilon RI engagement, tyrosine phosphorylation of SLP-76, PLC-gamma 1, and PLC-gamma 2 and calcium mobilization were dramatically reduced. LAT-deficient BMMCs also exhibited profound defects in activation of MAPK, degranulation, and cytokine production after Fc epsilon RI cross-linking. These results show that LAT plays a critical role in Fc epsilon RI-mediated signaling in mast cells.