The mitogen-activated protein kinase p38 regulates activator protein 1 by direct phosphorylation of c-Jun
The mitogen-activated protein kinase p38 regulates activator protein 1 by direct phosphorylation of c-Jun
复制标题
DOI：
10.1016/j.biocel.2007.06.013
复制
发表时间：
2007-01-01
影响因子：
4
通讯作者：
Pannen, Benedikt H. J.
中科院分区：
文献类型：
--
作者：
Humar, Matjaz;Loop, Torsten;Pannen, Benedikt H. J.
p38参与基本的生理过程，以及失调常常导致疾病的事实表明p38依赖性机制的潜在影响。在这里，我们证明了一个新的途径，包括诱导的促分裂原活化蛋白激酶p38蛋白激酶C和结果在一个特定的磷酸化的c-Jun在T淋巴细胞。P38直接磷酸化c-Jun在其反式激活结构域中的丝氨酸63和丝氨酸73，因此posturanscriptionally影响DNA结合的磷酸化c-Jun的存在，这是激活蛋白I依赖性基因转录的先决条件。此外，c-Fos、FosB和JunB的DNA结合活性也依赖于p38蛋白激酶活性，而JunD、Fra-1和Fra-2不受影响。虽然我们表明，应激诱导的丝裂原活化蛋白激酶共享c-Jun作为磷酸化的底物，p38介导的作用不能被c-Jun N-末端激酶拯救。这表明蛋白激酶p38在翻译后c-Jun调控中发挥独特且非冗余的作用。p38依赖性c-Jun磷酸化的诱导在CD 4+和CD 8（+）T细胞中是相当的，提出了一种与T细胞亚型和效应功能无关的普遍存在的途径。相比之下，ATF-2主要在CD 8（+）T细胞中磷酸化。不同的细胞系显示p38依赖性c-Jun磷酸化佛波醇酯诱导后，但有证据表明，猿猴病毒40大T抗原可能会干扰这一途径。(C)2007爱思唯尔有限公司保留所有权利。
The involvement of p38 in fundamental physiological processes and the fact that deregulation often leads to disease indicates the potential impact of p38 dependent mechanisms. Here we demonstrate a new pathway that includes the induction of the mitogen activated protein kinase p38 by protein kinase C and results in a specific phosphorylation of c-Jun in T-lymphocytes. P38 directly phosphorylates c-Jun within its transactivation domain at serine 63 and serine 73 and thus posuranscriptionally affects the presence of DNA-bound phosphorylated c-Jun, a prerequisite for activator protein I dependent gene transcription. Moreover, DNA-binding activity of c-Fos, FosB, and JunB were also dependent on the p38 protein kinase activity, whereas JunD, Fra-1 and Fra-2 were not affected. Although we show that stress induced mitogen activated protein kinases share c-Jun as a substrate for phosphorylation, p38 mediated effects could not be rescued by the c-Jun N-terminal kinases. This demonstrates that the protein kinase p38 plays a unique and non-redundant role in posttranslational c-Jun regulation. The induction of a p38 dependent c-Jun phosphorylation was comparable in both CD4+ and CD8(+) T-cells, proposing a ubiquitous pathway that is not linked to T-cell subtype and effector function. In contrast, ATF-2 was predominantly phosphorylated in CD8(+) T-cells. Different cell lines show p38-dependent c-Jun phosphorylation upon phorbol ester induction but there is evidence that the simian virus 40 large T-antigen may interfere with this pathway. (C) 2007 Elsevier Ltd. All rights reserved.