The small GTP-binding protein RhoA regulates a delayed rectifier potassium channel
The small GTP-binding protein RhoA regulates a delayed rectifier potassium channel
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DOI：
10.1016/s0092-8674(00)81212-x
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发表时间：
1998-06-12
期刊：
影响因子：
64.5
通讯作者：
Peralta, EG
中科院分区：
文献类型：
--
作者：
Cachero, TG;Morielli, AD;Peralta, EG
G蛋白偶联受体激活的酪氨酸激酶可以磷酸化，从而抑制延迟整流钾通道Kv1.2的活性。通过酵母双杂交筛选，我们确定了小的gtp结合蛋白RhoA是这一过程的必要成分。共免疫沉淀实验证实RhoA与Kv1.2相关。电生理分析显示，RhoA过表达显著降低了爪蟾卵母细胞中Kv1.2表达产生的基底电流。此外，在表达Kv1.2和m1毒蕈碱乙酰胆碱受体的293细胞中，使用C3外酶灭活RhoA可阻断mi受体抑制Kv1.2电流的能力。因此，这些结果表明，RhoA调节Kv1.2的活性，是受体介导的酪氨酸激酶依赖性Kv1.2抑制机制的核心组成部分。
Tyrosine kinases activated by G protein-coupled receptors can phosphorylate and thereby suppress the activity of the delayed rectifier potassium channel Kv1.2. Using a yeast two-hybrid screen, we identified the small GTP-binding protein RhoA as a necessary component in this process. Coimmunoprecipitation experiments confirmed that RhoA associates with Kv1.2. Electrophysiological analyses revealed that overexpression of RhoA markedly reduced the basal current generated by Kv1.2 expressed in Xenopus oocytes. Furthermore, in 293 cells expressing Kv1.2 and m1 muscarinic acetylcholine receptors, inactivating RhoA using C3 exoenzyme blocked the ability of mi receptors to suppress Kv1.2 current. Therefore, these results demonstrate that RhoA regulates Kv1.2 activity and is a central component in the mechanism of receptor-mediated tyrosine kinase-dependent suppression of Kv1.2.