• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >RhoH modulates pre-TCR and TCR signalling by regulating LCK
【24h】

RhoH modulates pre-TCR and TCR signalling by regulating LCK

机译：RhoH通过调节LCK来调节pre-TCR和TCR信号

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Pre-T-cell receptor (pre-TCR) and TCR signals govern the development of T-lymphocytes. RhoH, a hematopoietic-specific and GTPase-deficient member of the RhoGTPase family, is required in the development of T-lymphocytes. Here we found that RhoH binds and modulates LCK, the non-receptor tyrosine kinase crucial in initiating pre-TCR and TCR signallings. In both pre-TCR and TCR signalling transduction, LCK is phosphorylated by CSK to maintain the inactive state of LCK at rest. Upon being activated, CSK phosphorylation is removed and LCK autophosphorylation leads to LCK activation and further phosphorylates ZAP70 to initiate further downstream signalling. At rest, LCK may be recruited to the plasma membrane by RhoH, which also binds CSK, resulting in LCK inactivation. Additionally, the presence of RhoH enhances the inactivation phosphorylation of LCK by CSK. RhoH was found to bind preferentially inactive LCK, indicating that, upon ligand-mediated TCR activation, LCK is dephosphorylated resulting in LCK autoactivation and its release from RhoH. Thus RhoH is a critical part of the microenvironment for maintaining the inactive state of LCK. Furthermore, we found that the reduction of RhoH levels results in LCK autoactivation and constitutive activation of the TCR pathway. Our findings indicate that RhoH is a key adapter protein that maintains LCK in the inactive state, contributing to the regulation of both pre-TCR and TCR signalling during T-cell development. The data also supports a model for ligand-independent signal transduction by pre-TCR.
机译：前T细胞受体（pre-TCR）和TCR信号控制着T淋巴细胞的发育。 RhoH是RhoGTPase家族的造血特异性GTPase缺陷型成员，在T淋巴细胞的发育中是必需的。在这里，我们发现RhoH结合并调节LCK，这是非受体酪氨酸激酶，对启动TCR和TCR之前的信号至关重要。在TCR前和TCR信号转导中，LCK都会使LCK磷酸化，从而保持LCK处于静止状态。激活后，CSK磷酸化被去除，LCK自磷酸化导致LCK激活，并进一步磷酸化ZAP70以启动进一步的下游信号传导。静止时，LCH可能被RhoH募集到质膜上，而RhoH也与CSK结合，导致LCK失活。另外，RhoH的存在增强了CSK对LCK的灭活磷酸化作用。发现RhoH优先结合无活性的LCK，这表明在配体介导的TCR激活后，LCK被去磷酸化，导致LCK自激活并从RhoH中释放出来。因此，RhoH是维持LCK处于非活性状态的微环境的关键部分。此外，我们发现RhoH水平的降低导致LCR自动激活和TCR途径的组成型激活。我们的发现表明，RhoH是一种关键的衔接子蛋白，可将LCK维持在非活性状态，有助于在T细胞发育过程中同时调节TCR和TCR信号传导。数据还支持通过pre-TCR进行与配体无关的信号转导的模型。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号