Multiple phosphorylation sites in the 165-kilodalton peptide associated with dihydropyridine-sensitive calcium channels.
Multiple phosphorylation sites in the 165-kilodalton peptide associated with dihydropyridine-sensitive calcium channels.
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165 千道尔顿肽中的多个磷酸化位点与二氢吡啶敏感钙通道相关。
DOI：
10.1021/bi00416a036
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发表时间：
1988
期刊：
影响因子：
2.9
通讯作者：
Hosey,MM
中科院分区：
文献类型：
--
作者：
O'Callahan,CM;Hosey,MM
1988年4月22日收到的修订稿件摘要：来自电生理和离子通量研究的证据表明，二氢吡啶敏感的钙通道受神经递质介导的磷酸化和去磷酸化反应的调节。在本研究中，我们进一步鉴定了cAMP依赖的蛋白激酶和多功能的钙/钙调蛋白依赖的蛋白激酶的磷酸化，该165 kDa多肽膜相关形式被鉴定为骨骼肌二氢吡啶受体。与已建立的酶底物的磷酸化速率相比，两种蛋白激酶对165 kDa多肽的初始磷酸化速率被发现是相对较好的。这两种蛋白激酶对165 kDa多肽的磷酸化是相加的。先前被任何一种蛋白激酶单独磷酸化并不排除第二种蛋白激酶的磷酸化。CAMP依赖的蛋白激酶优先在丝氨酸残基上磷酸化165 kDa的多肽，但也形成少量的磷酸苏氨酸。相反，在膜/钙调蛋白依赖的蛋白激酶对165 kDa的多肽进行磷酸化后，回收的磷酸苏氨酸略多于磷酸丝氨酸。磷酸肽图显示，这两种激酶会在不同或相似的位置磷酸化多肽。值得注意的是，一个被cAMP依赖的蛋白激酶磷酸化的主要位点不被钙/钙调蛋白依赖的蛋白激酶磷酸化，而其他的位点被钙/钙调蛋白依赖的蛋白激酶高度磷酸化，但被cAMP依赖的蛋白激酶磷酸化的程度要小得多。结果表明，来自骨骼肌的165 kDa二氢吡啶受体可被cAMP和钙/钙调蛋白依赖的蛋白激酶在不同的位点上倍增磷酸化。由于165 kDa多肽可能是二氢吡啶敏感的钙通道的主要功能单位，这些结果提示神经递质对钙通道活性的磷酸化调节可能涉及到165 kDa多肽在多个位点的磷酸化。
Revised Manuscript Received April 22, 1988 abstract: Evidence from electrophysiological and ion flux studies has established that dihydropyridine-sensitive calcium channels are subject to regulation by neurotransmitter-mediated phosphorylation and dephosphorylation reactions. In the present study, we have further characterized the phosphorylation by cAMP-dependent protein kinaseand a multifunctional Ca/calmodulin-dependent protein kinase of the membrane-associated form of the 165-kDa polypeptide identified as the skeletal muscle dihydropyridine receptor. The initial rates of phosphorylation of the 165-kDa peptide by both protein kinases were found to be relatively good compared to the rates of phosphorylation of established substrates of the enzymes. Phosphorylation of the 165-kDa peptide by both protein kinases was additive. Prior phosphorylation by either one of the kinases alone did not preclude phosphorylation by the second kinase. The cAMP-dependent protein kinase phosphorylated the 165-kDa peptide preferentially at serine residues, although a small amount of phosphothreonine was also formed. In contrast, after phosphorylation of the 165-kDa peptide by theCa/calmodulin-dependent protein kinase, slightly more phosphothreonine than phosphoserine was recovered. Phosphopeptide mapping indicatedthat thetwo kinases phosphorylated the peptide at distinct as well as similar sites. Notably, one major site phosphorylated by the cAMP-dependent protein kinase was not phosphorylated by the Ca/calmodulin-dependent protein kinase, while other sites were phosphorylated to a high degree by the Ca/calmodulin-dependent protein kinase, butto a much lesser degree by the cAMP-dependent protein kinase. The results show that the 165-kDa dihydropyridine receptor from skeletal muscle can be multiply phosphorylated at distinct sites by the cAMP-and Ca/calmodulin-dependent protein kinases. As the 165-kDa peptide may be the major functional unitof the dihydropyridine-sensitive Ca channel, the results suggest that the phosphorylation-dependent modulation of Ca channel activity by neurotransmitters may involve phosphorylation of the 165-kDa peptide at multiple sites.
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DOI：
10.1073/pnas.83.19.7513
发表时间：
1986-10
影响因子：
11.1
作者：
J. Galizzi;M. Fosset;G. Romey;P. Laduron;M. Lazdunski
通讯作者：
J. Galizzi;M. Fosset;G. Romey;P. Laduron;M. Lazdunski
β-肾上腺素能效应器和环 AMP 对尼群地平敏感的骨骼肌电压依赖性 Ca2+ 通道的短期和长期影响。
影响因子：
4.8
作者：
A. Schmid;J. Renaud;M. Lazdunski
通讯作者：
M. Lazdunski
蛋白激酶 C 使乙酰胆碱受体磷酸化，并鉴定受体 δ 亚基内的磷酸化位点。
DOI：
10.1016/s0021-9258(18)60990-1
发表时间：
1987
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
A. Safran;R. Sagi;D. Neumann;S. Fuchs
通讯作者：
S. Fuchs
DOI：
10.1111/j.1432-1033.1984.tb08451.x
发表时间：
1984
期刊：
European journal of biochemistry
影响因子：
--
作者：
J. Galizzi;M. Fosset;M. Lazdunski
通讯作者：
M. Lazdunski
多功能钙调蛋白依赖性蛋白激酶的底物特异性。
DOI：
10.1016/s0021-9258(17)38593-9
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Pearson;J. Woodgett;P. Cohen;B. Kemp
通讯作者：
B. Kemp