...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF.
【24h】

Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF.

机译：Galpha 12通过酪氨酸磷酸化白血病相关的RhoGEF激活Rho GTPase。

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

Heterotrimeric G proteins, G12 and G13, have been shown to transduce signals from G protein-coupled receptors to activate Rho GTPase in cells. Recently, we identified p115RhoGEF, one of the guanine nucleotide exchange factors (GEFs) for Rho, as a direct link between Galpha13 and Rho [Kozasa, T., et al. (1998) Science 280, 2109-2111; Hart, M. J., et al. (1998) Science 280, 2112-2114]. Activated Galpha13 stimulated the RhoGEF activity of p115 through interaction with the N-terminal RGS domain. However, Galpha12 could not activate Rho through p115, although it interacted with the RGS domain of p115. The biochemical mechanism from Galpha12 to Rho activation remained unknown. In this study, we analyzed the interaction of leukemia-associated RhoGEF (LARG), which also contains RGS domain, with Galpha12 and Galpha13. RGS domain of LARG demonstrated Galpha12- and Galpha13-specific GAP activity. LARG synergistically stimulated SRF activation by Galpha12 and Galpha13 in HeLa cells, and the SRF activation by Galpha12-LARG was further stimulated by coexpression of Tec tyrosine kinase. It was also found that LARG is phosphorylated on tyrosine by Tec. In reconstitution assays, the RhoGEF activity of nonphosphorylated LARG was stimulated by Galpha13 but not Galpha12. However, when LARG was phosphorylated by Tec, Galpha12 effectively stimulated the RhoGEF activity of LARG. These results demonstrate the biochemical mechanism of Rho activation through Galpha12 and that the regulation of RhoGEFs by heterotrimeric G proteins G1213 is further modulated by tyrosine phosphorylation.
机译：异源三聚体G蛋白G12和G13可以转导来自G蛋白偶联受体的信号，从而激活细胞中的Rho GTPase。最近，我们将p115RhoGEF（Rho的鸟嘌呤核苷酸交换因子（GEF）之一）鉴定为Galpha13和Rho之间的直接链接[Kozasa，T.等。 （1998）Science 280，2109-2111； Hart，M.J。等。 （1998）Science 280，2112-2114]。活化的Galpha13通过与N末端RGS结构域的相互作用刺激了p115的RhoGEF活性。但是，尽管Galpha12与p115的RGS结构域相互作用，但它无法通过p115激活Rho。从Galpha12到Rho激活的生化机制仍然未知。在这项研究中，我们分析了白血病相关的RhoGEF（LARG）与Galpha12和Galpha13的相互作用，后者还包含RGS域。 LARG的RGS域显示Galpha12和Galpha13特异的GAP活性。 LARG协同刺激HeLa细胞中Galpha12和Galpha13激活SRF激活，并且Tec酪氨酸激酶的共表达进一步刺激Galpha12-LARG激活SRF。还发现，Tec使LARG在酪氨酸上磷酸化。在重组测定中，非磷酸化的LARG的RhoGEF活性受Galpha13刺激，但不受Galpha12刺激。但是，当LARG被Tec磷酸化时，Galpha12有效地刺激了LARG的RhoGEF活性。这些结果证明了通过Galpha12激活Rho的生物化学机制，以及酪氨酸磷酸化进一步调节了异源三聚G蛋白G1213对RhoGEF的调控。

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