REGULATION OF BRAIN TYPE-II CA-2+ CALMODULIN-DEPENDENT PROTEIN-KINASE BY AUTOPHOSPHORYLATION - A CA-2+-TRIGGERED MOLECULAR SWITCH
REGULATION OF BRAIN TYPE-II CA-2+ CALMODULIN-DEPENDENT PROTEIN-KINASE BY AUTOPHOSPHORYLATION - A CA-2+-TRIGGERED MOLECULAR SWITCH
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DOI：
10.1016/0092-8674(86)90008-5
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发表时间：
1986-03-28
期刊：
影响因子：
64.5
通讯作者：
KENNEDY, MB
中科院分区：
文献类型：
--
作者：
MILLER, SG;KENNEDY, MB
钙/钙调蛋白刺激的一种重要的脑钙调素依赖蛋白激酶(II型钙调蛋白激酶)的自动磷酸化导致其酶活性的急剧变化。这些变化表明了一种机制，通过这种机制，该激酶可以充当钙触发的分子开关。每种全酶可能有30个磷酸基团，其中3-12个基团的掺入会导致对外源底物的激酶活性以及自我磷酸化本身变得不依赖于钙。因此，在最初激活钙信号的持续时间之后，可以延长激酶的活性。钙非依赖性的自磷酸化可以通过对抗细胞内磷酸酶的去磷酸化而进一步延长活性状态。
Calcium/calmodulin-stimulated autophosphorylation of a prominent brain calmodulin-dependent protein kinase (Type II CaM kinase) produces dramatic changes in its enzymatic activity. These changes suggest a mechanism by which the kinase could act as a calcium-triggered molecular switch. Incorporation of 3-12 of a possible total of 30 phosphate groups per holoenzyme causes kinase activity toward exogenous substrates as well as autophosphorylation itself to become independent of calcium. Thus, kinase activity could be prolonged beyond the duration of an initial activating calcium signal. The calcium-independent autophosphorylation could further prolong the active state by opposing dephosphorylation by cellular phosphatases.