A Signaling Complex of Ca 2 1 -Calmodulin– Dependent Protein Kinase IV and Protein Phosphatase 2A
A Signaling Complex of Ca 2 1 -Calmodulin– Dependent Protein Kinase IV and Protein Phosphatase 2A
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发表时间：
1998
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通讯作者：
R. Westphal;K. A. Anderson;A. Means;B. Wadzinski
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作者：
R. Westphal;K. A. Anderson;A. Means;B. Wadzinski
刺激T淋巴细胞后，细胞内钙离子浓度([Ca21]i)迅速升高，与钙调蛋白依赖的蛋白激酶IV(CaMKIV)的激活平行，CaMKIV是一种核酶，可以磷酸化并激活环腺苷(CAMP)反应元件结合蛋白(CREB)。然而，尽管T细胞激活所需的[钙2 1]i持续增加，CaMKIV还是发生了失活。鉴定了CaMKIV与蛋白质丝氨酸苏氨酸磷酸酶2A(PP2A)的稳定的化学计量复合体，其中PP2A使CaMKIV去磷酸化，并作为CaMKIV信号的负调控因子。在Jurkat T细胞中，小t抗原抑制PP2A活性可增强CaMKIV对CREB介导的转录的激活作用。这些发现揭示了一种细胞内信号机制，即蛋白丝氨酸-苏氨酸激酶(CaMKIV)受紧密相关的蛋白丝氨酸-苏氨酸磷酸酶(PP2A)的调节。
Stimulation of T lymphocytes results in a rapid increase in intracellular calcium concentration ([Ca 2 1 ] i ) that parallels the activation of Ca 2 1 -calmodulin–dependent protein kinase IV (CaMKIV ), a nuclear enzyme that can phosphorylate and activate the cyclic adenosine monophosphate (cAMP) response element–binding protein (CREB). Howev-er, inactivation of CaMKIV occurs despite the sustained increase in [Ca 2 1 ] i that is required for T cell activation. A stable and stoichiometric complex of CaMKIV with protein serine-threonine phosphatase 2A (PP2A) was identified in which 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).