CALCIUM/CALMODULIN-DEPENDENT PROTEIN-KINASE TYPE-II AND TYPE-IV DIFFERENTIALLY REGULATE CREB-DEPENDENT GENE-EXPRESSION
CALCIUM/CALMODULIN-DEPENDENT PROTEIN-KINASE TYPE-II AND TYPE-IV DIFFERENTIALLY REGULATE CREB-DEPENDENT GENE-EXPRESSION
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DOI：
10.1128/mcb.14.9.6107
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发表时间：
1994-09-01
影响因子：
5.3
通讯作者：
MCKNIGHT, GS
中科院分区：
文献类型：
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作者：
MATTHEWS, RP;GUTHRIE, CR;MCKNIGHT, GS
cAMP 依赖性蛋白激酶 (PKA) 磷酸化 CREB（环 AMP [cAMP]- 反应元件 [CRE] 结合蛋白）会导致许多含有 CRE 的启动子被激活。在神经元和其他细胞类型中，CREB 磷酸化和含有 CRE 的启动子的激活可以响应细胞内 Ca2+ 的升高而发生。在通常缺乏这种 Ca2+ 反应性的培养细胞中，我们通过引入 Ca2+/钙调蛋白依赖性蛋白激酶 IV 型 (CaMKIV) 的表达载体来赋予 Ca2+ 介导的含有 CRE 的启动子的激活。激活也可以由不依赖 Ca2+ 的 CaMKIV 组成型活性形式直接介导。 CaMKIV 介导的基因诱导需要 CREB/ATF 家族成员的活性，但独立于 PKA 活性。相比之下，组成型活性或野生型 Ca2+/钙调蛋白依赖性蛋白激酶 II (CaMKII) 的瞬时表达无法介导相同的含有 CRE 的报告基因的反式激活。对瞬时表达的 CaMKIV 和 CaMKII 的亚细胞分布的检查表明，只有 CaMKIV 进入细胞核。我们的结果表明，在神经元、生殖和淋巴组织中表达的 CaMKIV 可能充当 Ca2+ 依赖性基因诱导的介质。
Phosphorylation of CREB (cyclic AMP [cAMP]- response element [CRE]-binding protein) by cAMP-dependent protein kinase (PKA) leads to the activation of many promoters containing CREs. In neurons and other cell types, CREB phosphorylation and activation of CRE containing promoters can occur in response to elevated intracellular Ca2+ In cultured cells that normally lack this Ca2+ responsiveness, we confer Ca2+-mediated activation of a CRE containing promoter by introducing an expression vector for Ca2+/calmodulin-dependent protein kinase type IV (CaMKIV). Activation could also be mediated directly by a constitutively active form of CaMKIV which is Ca2+ independent. The CaMKIV-mediated gene induction requires the activity of CREB/ATF family members but is independent of PKA activity. In contrast, transient expression of either a constitutively active or wild-type Ca2+/calmodulin-dependent protein kinase type II (CaMKII) fails to mediate the transactivation of the same CRE-containing reporter gene. Examination of the subcellular distribution of transiently expressed CaMKIV and CaMKII reveals that only CaMKIV enters the nucleus. Our results demonstrate that CaMKIV, which is expressed in neuronal, reproductive, and lymphoid tissues, may act as a mediator of Ca2+-dependent gene induction.