CREB - A CA2+-REGULATED TRANSCRIPTION FACTOR PHOSPHORYLATED BY CALMODULIN-DEPENDENT KINASES
CREB - A CA2+-REGULATED TRANSCRIPTION FACTOR PHOSPHORYLATED BY CALMODULIN-DEPENDENT KINASES
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DOI：
10.1126/science.1646483
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发表时间：
1991-06-07
期刊：
影响因子：
56.9
通讯作者：
GREENBERG, ME
中科院分区：
文献类型：
--
作者：
SHENG, M;THOMPSON, MA;GREENBERG, ME
研究了钙离子在膜去极化反应中介导基因诱导的机制。3‘，5’-单磷酸腺苷(CAMP)反应元件结合蛋白(CREB)是一种钙离子调节的转录因子，也是去极化激活的钙钙调素依赖的蛋白激酶(CaM)I和II的底物。在体外，CREB残基Ser133是CaM激酶的主要磷酸化位点，在体内则是膜去极化后的磷酸化。Ser133突变使CREB对钙离子的反应能力减弱。这些结果表明，CaM激酶可能将电信号传递到核内，CREB具有整合钙和cAMP信号的功能。
The mechanism by which Ca2+ mediates gene induction in response to membrane depolarization was investigated. The adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB) was shown to function as a Ca2+-regulated transcription factor and as a substrate for depolarization-activated Ca2+-calmodulin-dependent protein kinases (CaM kinases) I and II. CREB residue Ser133 was the major site of phosphorylation by the CaM kinases in vitro and of phosphorylation after membrane depolarization in vivo. Mutation of Ser133 impaired the ability of CREB to respond to Ca2+. These results suggest that CaM kinases may transduce electrical signals to the nucleus and that CREB functions to integrate Ca2+ and cAMP signals.