ELIMINATION OF RAPID POTASSIUM CHANNEL INACTIVATION BY PHOSPHORYLATION OF THE INACTIVATION GATE
ELIMINATION OF RAPID POTASSIUM CHANNEL INACTIVATION BY PHOSPHORYLATION OF THE INACTIVATION GATE
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DOI：
10.1016/0896-6273(94)90425-1
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发表时间：
1994-12-01
期刊：
影响因子：
16.2
通讯作者：
VYAS, TB
中科院分区：
文献类型：
--
作者：
COVARRUBIAS, M;WEI, AA;VYAS, TB
蛋白激酶C（PKC）对K+通道的快速N型失活的影响以前未见报道。我们发现，PKC特异性地消除了克隆的人A型K+通道（hKv3.4）的快速失活，将该通道从快速失活的A型转换为非失活的延迟整流型。生化分析表明，hKv3.4的N-末端结构域在体外被PKC磷酸化，诱变实验表明，在N-末端的失活门内的两个丝氨酸是直接PKC作用的位点。此外，将这些丝氨酸之一突变为天冬氨酸模拟PKC的作用。因此，丝氨酸磷酸化可以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。这里报道的调节机制可能对神经系统中的信号编码有实质性的影响。
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.