A PHOSPHORYLATION SITE IN THE NA+ CHANNEL REQUIRED FOR MODULATION BY PROTEIN-KINASE-C
A PHOSPHORYLATION SITE IN THE NA+ CHANNEL REQUIRED FOR MODULATION BY PROTEIN-KINASE-C
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DOI：
10.1126/science.1658937
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发表时间：
1991-11-08
期刊：
影响因子：
56.9
通讯作者：
CATTERALL, WA
中科院分区：
文献类型：
--
作者：
WEST, JW;NUMANN, R;CATTERALL, WA
电压门控钠通道负责在可兴奋细胞中产生动作电位。蛋白激酶C的激活减缓了钠通道的失活并降低了峰值钠电流。磷酸化的一个单一的残基，丝氨酸1506，这是位于保守的胞内环之间的域III和IV，并参与失活的钠通道，是必需的两个调节作用。缺乏该磷酸化位点的突变钠通道在未受刺激的细胞中具有正常的功能特性，但对蛋白激酶C的激活不应答。钠通道α亚基中这个保守位点的磷酸化可以调节广泛的可兴奋细胞中的电活动。
Voltage-gated sodium channels are responsible for generation of action potentials in excitable cells. Activation of protein kinase C slows inactivation of sodium channels and reduces peak sodium currents. Phosphorylation of a single residue, serine 1506, that is located in the conserved intracellular loop between domains III and IV and is involved in inactivation of the sodium channel, is required for both modulatory effects. Mutant sodium channels lacking this phosphorylation site have normal functional properties in unstimulated cells but do not respond to activation of protein kinase C. Phosphorylation of this conserved site in sodium channel alpha-subunits may regulate electrical activity in a wide range of excitable cells.