通过失活门的磷酸化消除快速钾通道失活。
Elimination of rapid potassium channel inactivation by phosphorylation of the inactivation gate.
作者信息
Covarrubias M, Wei A, Salkoff L, Vyas T B
机构信息
Department of Anatomy, Pathology, and Cell Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107.
出版信息
Neuron. 1994 Dec;13(6):1403-12. doi: 10.1016/0896-6273(94)90425-1.
Abstract
The effect of protein kinase C (PKC) on rapid N-type inactivation of K+ channels has not been reported previously. We found that PKC specifically eliminates rapid inactivation of a cloned human A-type K+ channel (hKv3.4), converting this channel from a rapidly inactivating A type to a noninactivating delayed rectifier type. Biochemical analysis showed that the N-terminal domain of hKv3.4 is phosphorylated in vitro by PKC, and mutagenesis experiments revealed that two serines within the inactivation gate at the N-terminus are sites of direct PKC action. Moreover, mutating one of these serines to aspartic acid mimics the action of PKC. Serine phosphorylation may thus prevent rapid inactivation by shielding basic residues known to be critical to the function of the inactivation gate. The regulatory mechanism reported here may have substantial effects on signal coding in the nervous system.
摘要
蛋白激酶C（PKC）对钾通道快速N型失活的影响此前尚未见报道。我们发现，PKC特异性消除克隆的人类A型钾通道（hKv3.4）的快速失活，将该通道从快速失活的A型转变为非失活的延迟整流型。生化分析表明，hKv3.4的N端结构域在体外被PKC磷酸化，诱变实验显示，N端失活门内的两个丝氨酸是PKC直接作用的位点。此外，将其中一个丝氨酸突变为天冬氨酸可模拟PKC的作用。因此，丝氨酸磷酸化可能通过屏蔽已知对失活门功能至关重要的碱性残基来防止快速失活。此处报道的调节机制可能对神经系统中的信号编码产生重大影响。
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