cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1.

Leonard AS; Yermolaieva O; Hruska Hageman A; Askwith CC; Price MP; Wemmie JA; Welsh MJ

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cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1.

机译：酸敏感离子通道1的cAMP依赖性蛋白激酶磷酸化调节其与与C激酶1相互作用的蛋白的结合。

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The acid-sensing ion channel-1 (ASIC1) contributes to synaptic plasticity and may influence the response to cerebral ischemia and acidosis. We found that cAMP-dependent protein kinase phosphorylated heterologously expressed ASIC1 and endogenous ASIC1 in brain slices. ASIC1 also showed significant phosphorylation under basal conditions. Previous studies showed that the extreme C-terminal residues of ASIC1 bind the PDZ domain of the protein interacting with C-kinase-1 (PICK1). We found that protein kinase A phosphorylation of Ser-479 in the ASIC1 C terminus interfered with PICK1 binding. In contrast, minimizing phosphorylation or mutating Ser-479 to Ala enhanced PICK1 binding. Phosphorylation-dependent disruption of PICK1 binding reduced the cellular colocalization of ASIC1 and PICK1. Thus, the ASIC1 C terminus contains two sites that influence its binding to PICK1. Regulation of this interaction by phosphorylation provides a mechanism to control the cellular localization of ASIC1.

机译：酸敏感离子通道1（ASIC1）有助于突触可塑性，并可能影响对脑缺血和酸中毒的反应。我们发现，cAMP依赖性蛋白激酶在脑切片中磷酸化异源表达ASIC1和内源性ASIC1。在基础条件下，ASIC1也显示出明显的磷酸化。先前的研究表明，ASIC1的极端C末端残基结合了与C激酶1（PICK1）相互作用的蛋白质的PDZ结构域。我们发现ASIC1 C末端的蛋白激酶A Ser-479的磷酸化干扰了PICK1的结合。相反，最小化磷酸化或将Ser-479突变为Ala可增强PICK1的结合。 PICK1结合的磷酸化依赖性破坏降低了ASIC1和PICK1的细胞共定位。因此，ASIC1 C末端包含两个位点，这些位点会影响其与PICK1的结合。通过磷酸化调节这种相互作用提供了一种机制来控制ASIC1的细胞定位。

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《Proceedings of the National Academy of Sciences of the United States of America》 |2003年第4期|P.2029-2034|共6页
作者
Leonard AS; Yermolaieva O; Hruska Hageman A; Askwith CC; Price MP; Wemmie JA; Welsh MJ;
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作者单位

Departments of Internal Medicine, Psychiatry, and Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242.;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种 eng
中图分类自然科学总论;
关键词
ASIC1; Phosphorylation; Carbon ion; binding; 8-chloro-cyclic adenosine monophosphate; 磷酰化;

机译：ASIC1;磷酸化;碳离子;捆绑;8-氯环一磷酸腺苷;磷酰化;

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6. cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1 [O] . A. Soren Leonard, Olena Yermolaieva, Alesia Hruska-Hageman, 2003

机译：酸敏感离子通道1的cAMP依赖性蛋白激酶磷酸化调节其与与C激酶1相互作用的蛋白的结合
7. cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1 [O] . Leonard, A. Soren, Yermolaieva, Olena, Hruska-Hageman, Alesia, 2003

机译：酸敏感离子通道1的cAMP依赖性蛋白激酶磷酸化调节其与与C激酶1相互作用的蛋白的结合

cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1.

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