RhoH is important for positive thymocyte selection and T-cell receptor signaling
RhoH is important for positive thymocyte selection and T-cell receptor signaling
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DOI：
10.1182/blood-2006-04-019034
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发表时间：
2007-03-15
期刊：
影响因子：
20.3
通讯作者：
Brakebusch, Cord
中科院分区：
文献类型：
--
作者：
Dorn, Tatjana;Kuhn, Ursula;Brakebusch, Cord
RhoH是一种仅在造血系统中表达的小GTPase。通过使用靶向破坏RhoH基因的小鼠，我们证明了RhoH在DN3到DN4转换和阳性选择过程中对胸腺细胞成熟至关重要。此外，DN3和DN4胸腺细胞在体外分化和扩增严重受损。这些缺陷与TCR信号的缺陷相对应。虽然RhoH不是tcr诱导的ZAP70激活和ZAP70介导的p38激活所必需的，但它对于LAT、PLC γ 1和Vav1的酪氨酸磷酸化以及Erk和钙内流的激活至关重要。这些数据表明RhoH对TCR前和TCR信号传导很重要，因为它允许ZAP70与LAT信号体有效相互作用，从而调节胸腺细胞的发育。
RhoH is a small GTPase expressed only in the hematopoletic system. With the use of mice with targeted disruption of the RhoH gene, we demonstrated that RhoH is crucial for thymocyte maturation during DN3 to DN4 transition and during positive selection. Furthermore, the differentiation and expansion of DN3 and DN4 thymocytes in vitro were severely impaired. These defects corresponded to defective TCR signaling. Although RhoH is not required for TCR-induced activation of ZAP70 and ZAP70-mediated activation of p38, it is crucial for the tyrosine phosphorylation of LAT, PLC gamma 1, and Vav1 and for the activation of Erk and calcium influx. These data suggest that RhoH is important for pre-TCR and TCR signaling because it allows the efficient interaction of ZAP70 with the LAT signalosome, thus regulating thymocyte development.