RhoH GTPase recruits and activates Zap70 required for T cell receptor signaling and thymocyte development
RhoH GTPase recruits and activates Zap70 required for T cell receptor signaling and thymocyte development
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DOI：
10.1038/ni1396
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发表时间：
2006-11-01
影响因子：
30.5
通讯作者：
Williams, David A.
中科院分区：
文献类型：
--
作者：
Gu, Yi;Chae, Hee-Don;Williams, David A.
RhoH是Rho GTP酶家族的造血特异性GTP酶缺陷成员，具有未知的生理功能。在这里，我们证明，Rhoh（-/-）小鼠有受损的T细胞受体（TCR）介导的胸腺细胞的选择和成熟，导致T细胞缺陷。RhoH缺乏导致CD 3 zeta磷酸化缺陷，信号分子Zap 70向免疫突触的易位受损，并减少胸腺和外周T细胞中Zap 70介导的信号传导的激活。蛋白质组学分析表明，RhoH是TCR信号传导的一个组成部分，并且是通过与RhoH非经典免疫受体酪氨酸激活基序（ITAM）相互作用将Zap 70募集到TCR所必需的。体内重建研究还表明，RhoH功能依赖于RhoH ITAM的磷酸化。这些发现表明RhoH是胸腺细胞发育和TCR信号转导的关键调节因子，通过介导Zap 70的募集和激活。
RhoH is a hematopoietic-specific, GTPase-deficient member of the Rho GTPase family with unknown physiological function. Here we demonstrate that Rhoh(-/-) mice have impaired T cell receptor ( TCR)-mediated thymocyte selection and maturation, resulting in T cell deficiency. RhoH deficiency resulted in defective CD3 zeta phosphorylation, impaired translocation of the signaling molecule Zap70 to the immunological synapse and reduced activation of Zap70-mediated signaling in thymic and peripheral T cells. Proteomic analyses demonstrated that RhoH is a component of TCR signaling and is required for recruitment of Zap70 to the TCR through interaction with RhoH noncanonical immunoreceptor tyrosine-based activation motifs ( ITAMs). In vivo reconstitution studies also demonstrated that RhoH function depends on phosphorylation of the RhoH ITAMs. These findings suggest that RhoH is a critical regulator of thymocyte development and TCR signaling by mediating recruitment and activation of Zap70.