CLONED CA2+-DEPENDENT K+ CHANNEL MODULATED BY A FUNCTIONALLY ASSOCIATED PROTEIN-KINASE
CLONED CA2+-DEPENDENT K+ CHANNEL MODULATED BY A FUNCTIONALLY ASSOCIATED PROTEIN-KINASE
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DOI：
10.1038/369563a0
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发表时间：
1994-06-16
期刊：
影响因子：
64.8
通讯作者：
LEVITAN, IB
中科院分区：
文献类型：
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作者：
ESGUERRA, M;WANG, J;LEVITAN, IB
钙依赖钾(K-Ca)通道携带离子电流，调节重要的细胞功能(1-3)。与其他一些离子通道(4-10)一样，钾-钙通道受蛋白质磷酸化(2，11，15-21)的调节。最近克隆的编码Slo钾-钙通道(12-14)的互补DNA使钾-钙通道的调制得以研究。我们在这里报道了蛋白质磷酸化调节在非洲爪哇卵母细胞中表达的果蝇Slo钾-钙通道的活性。在分离的膜片上应用三磷酸腺苷-伽马S通过改变通道电压敏感性来增加Slo通道的活性。这种调节被一种特定的环磷酸腺苷依赖蛋白激酶(PKA)抑制剂所阻断。通道蛋白中单个丝氨酸残基的突变也阻止了三磷酸腺苷-伽马S的调节，证明了Slo通道蛋白本身的磷酸化调节通道活性。结果还表明，卵母细胞膜上的钾-钙通道可以被一种内源性的PKA样蛋白激酶所调节，它在功能上仍然与分离的膜上的钾-钙通道相关。
CALCIUM-DEPENDENT potassium (K-Ca) channels carry ionic currents that regulate important cellular functions(1-3). Like some other ion channels(4-10), K-Ca channels are modulated by protein phosphorylation(2,11,15-21). The recent cloning of complementary DNAs encoding Slo K-Ca channels(12-14) has enabled K-Ca channel modulation to be investigated. We report here that protein phosphorylation modulates the activity of Drosophila Slo K-Ca channels expressed in Xenopus oocytes. Application of ATP-gamma S to detached membrane patches increases Slo channel activity by shifting channel voltage sensitivity. This modulation is blocked by a specific inhibitor of cyclic AMP-dependent protein kinase (PKA). Mutation of a single serine residue in the channel protein also blocks modulation by ATP-gamma S, demonstrating that phosphorylation of the Slo channel protein itself modulates channel activity. The results also indicate that K-Ca channels in oocyte membrane patches can be modulated by an endogenous PKA-like protein kinase which remains functionally associated with the channels in the detached patch.