A signaling complex of Ca2+-calmodulin-dependent protein kinase IV and protein phosphatase 2A
A signaling complex of Ca2+-calmodulin-dependent protein kinase IV and protein phosphatase 2A
复制标题
DOI：
10.1126/science.280.5367.1258
复制
发表时间：
1998-05-22
期刊：
影响因子：
56.9
通讯作者：
Wadzinski, BE
中科院分区：
文献类型：
--
作者：
Westphal, RS;Anderson, KA;Wadzinski, BE
T淋巴细胞的刺激导致细胞内钙浓度（[Ca 2 +]（i））的快速增加，这与Ca 2 +-钙调蛋白依赖性蛋白激酶IV（CaMKIV）的激活平行，CaMKIV是一种可以磷酸化和激活环磷酸腺苷（cAMP）反应元件结合蛋白（CREB）的核酶。然而，尽管T细胞活化所需的[Ca 2 +]（i）持续增加，CaMKIV的失活仍会发生。CaM KIV与蛋白质丝氨酸-苏氨酸磷酸酶2A（PP 2A）的稳定和化学计量复合物被鉴定，其中PP 2A使CaMKIV去磷酸化并作为CaMKIV信号传导的负调节剂起作用。在Jurkat T细胞中，小t抗原抑制PP 2A活性增强了CaMKIV对CREB介导的转录的激活。这些发现揭示了细胞内信号传导机制，其中蛋白丝氨酸-苏氨酸激酶（CaMKIV）由紧密相关的蛋白丝氨酸-苏氨酸磷酸酶（PP 2A）调节。
Stimulation of T lymphocytes results in a rapid increase in intracellular calcium concentration ([Ca2+](i)) that parallels the activation of Ca2+-calmodulin-dependent protein kinase IV (CaMKIV), a nuclear enzyme that can phosphorylate and activate the cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB). However, inactivation of CaMKIV occurs despite the sustained increase in [Ca2+](i) that is required for T cell activation. A stable and stoichiometric complex of CaM KIV with protein serine-threonine phosphatase 2A (PP2A) was identified in wh ich PP2A dephosphorylates CaMKIV and functions as a negative regulator of CaMKIV signaling. In Jurkat T cells, inhibition of PP2A activity by small t antigen enhanced activation of CREB-mediated transcription by CaMKIV. These findings reveal an intracellular signaling mechanism whereby a protein serine-threonine kinase (CaMKIV) is regulated by a tightly associated protein serine-threonine phosphatase (PP2A).