c-Jun phosphorylation by the human vaccinia-related kinase 1 (VRK1) and its cooperation with the N-terminal kinase of c-Jun (JNK)
c-Jun phosphorylation by the human vaccinia-related kinase 1 (VRK1) and its cooperation with the N-terminal kinase of c-Jun (JNK)
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DOI：
10.1038/sj.onc.1208015
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发表时间：
2004-11-25
期刊：
影响因子：
8
通讯作者：
Lazo, PA
中科院分区：
文献类型：
--
作者：
Sevilla, A;Santos, CR;Lazo, PA
VRK1 激酶是人类激酶组中的一种新型 Ser-Thr 激酶，与酪蛋白激酶 1 分支不同。这些激酶磷酸化与应激反应相关的转录因子，例如 p53。在本报告中，我们研究了转录因子 c-Jun 在其 N 末端区域的磷酸化。 VRK1 蛋白以 0.4 muM 的 Km 磷酸化 c-Jun，且不受 SP600125 抑制。 VRK1 在体外磷酸化 c-Jun 的 Ser63 和 Ser73，这与 c-Jun N 端激酶 (JNK) 所靶向的残基相同。这种磷酸化诱导 c-Jun 蛋白的稳定和积累。 VRK1 磷酸化 Ser63 中的内源性 c-Jun。 VRK1 激活 c-Jun 依赖性转录，这依赖于 Ser63 和 Ser73 的磷酸化。当与 VRK1 共转染时，具有 Ser63Ala 和 Ser73Ala 取代的 c-Jun 不具有转录活性。 VRK1 与 c-Jun 相互作用，但不与 JNK 相互作用。 VRK1和JNK的共转染对c-Jun的转录激活具有累加效应，表明当两者都处于次优剂量时它们可以合作；否则，其中一个的最大效应会阻止另一个的效应。 VRK1-c-Jun 连接代表新信号通路的一个组成部分，其上游元件仍有待识别。
The VRK1 kinase is a novel Ser-Thr kinase in the human kinome that diverged from the casein kinase 1 branch. These kinases phosphorylate transcription factors related to stress responses, such as p53. In this report we have studied the phosphorylation of the transcription factor c-Jun in its N-terminal region. The VRK1 protein phosphorylates c-Jun with a Km of 0.4 muM, and is not inhibited by SP600125. VRK1 phosphorylates c-Jun in Ser63 and Ser73 in vitro, the same residues targeted by the N-terminal kinase of c-Jun (JNK). This phosphorylation induces the stabilization and accumulation of the c-Jun protein. VRK1 phosphorylates the endogenous c-Jun in Ser63. VRK1 activates c-Jun dependent transcription, which is dependent on phosphorylation of Ser63 and Ser73. The c-Jun with Ser63Ala and Ser73Ala substitutions is not transcriptionally active when cotransfected with VRK1. VRK1 interacts with c-Jun but not with JNK. The cotransfection of VRK1 and JNK has an additive effect on the transcriptional activation of c-Jun indicating that they can cooperate when both are at suboptimal dose; otherwise, maximum effect by one of them prevents the effect of the other. The VRK1-c-Jun connection represents a component of a new signaling pathway whose upstream elements remain to be identified.