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Tyrosine-kinase-dependent recruitment of RGS12 to the N-type calcium channel.

机译:酪氨酸激酶依赖的RGS12募集至N型钙通道。

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Gamma-aminobutyric acid (GABA)B receptors couple to Go to inhibit N-type calcium channels in embryonic chick dorsal root ganglion neurons. The voltage-independent inhibition, mediated by means of a tyrosine-kinase pathway, is transient and lasts up to 100 seconds. Inhibition of endogenous RGS12, a member of the family of regulators of G-protein signalling, selectively alters the time course of voltage-independent inhibition. The RGS12 protein, in addition to the RGS domain, contains PDZ and PTB domains. Fusion proteins containing the PTB domain of RGS12 alter the rate of termination of the GABA(B) signal, whereas the PDZ or RGS domains of RGS 12 have no observable effects. Using primary dorsal root ganglion neurons in culture, here we show an endogenous agonist-induced tyrosine-kinase-dependent complex of RGS12 and the calcium channel. These results indicate that RGS12 is a multifunctional protein capable of direct interactions through its PTB domain with the tyrosine-phosphorylated calcium channel. Recruitment of RGS proteins to G-protein effectors may represent an additional mechanism for signal termination in G-protein-coupled pathways.
机译:γ-氨基丁酸(GABA)B受体与Go结合,以抑制胚胎雏鸡背根神经节神经元中的N型钙通道。通过酪氨酸激酶途径介导的电压非依赖性抑制是短暂的,持续长达100秒。内源性RGS12(G蛋白信号调节因子家族的成员)的抑制作用选择性地改变了电压依赖性抑制作用的时间过程。除了RGS结构域之外,RGS12蛋白还包含PDZ和PTB结构域。包含RGS12的PTB结构域的融合蛋白会改变GABA(B)信号的终止速率,而RGS 12的PDZ或RGS结构域则没有可观察到的作用。在培养中使用初级背根神经节神经元,在这里我们显示内源性激动剂诱导的酪氨酸激酶依赖性复合物RGS12和钙通道。这些结果表明RGS12是一种多功能蛋白,能够通过其PTB结构域与酪氨酸磷酸化钙通道直接相互作用。 RGS蛋白向G蛋白效应子的募集可能代表G蛋白偶联途径中信号终止的另一种机制。

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