PRO-INFLAMMATORY CYTOKINES AND ENVIRONMENTAL-STRESS CAUSE P38 MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVATION BY DUAL PHOSPHORYLATION ON TYROSINE AND THREONINE
PRO-INFLAMMATORY CYTOKINES AND ENVIRONMENTAL-STRESS CAUSE P38 MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVATION BY DUAL PHOSPHORYLATION ON TYROSINE AND THREONINE
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DOI：
10.1074/jbc.270.13.7420
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发表时间：
1995-03-31
影响因子：
4.8
通讯作者：
DAVIS, RJ
中科院分区：
文献类型：
--
作者：
RAINGEAUD, J;GUPTA, S;DAVIS, RJ
通过Tyr和Thr上的双重磷酸化激活的蛋白激酶（MAP激酶）可以分为两大类：ERK和JNK。ERR组通过Ras依赖性机制调节响应于生长因子的多个靶点。相反，JNK激活响应于促炎细胞因子和细胞暴露于几种形式的环境应激的转录因子c-Jun。最近，鉴定了与促分裂原活化蛋白（MAP）激酶共享序列相似性的新型哺乳动物蛋白激酶（p38）。p38的活化机制是由Thr-180和Tyr-182上的双重磷酸化介导的。免疫荧光显微镜证实p38 MAP激酶存在于活化细胞的细胞核和细胞质中。
Protein kinases activated by dual phosphorylation on Tyr and Thr (MAP kinases) can be grouped into two major classes: ERK and JNK. The ERR group regulates multiple targets in response to growth factors via a Ras-dependent mechanism, In contrast, JNK activates the transcription factor c-Jun in response to pro-inflammatory cytokines and exposure of cells to several forms of environmental stress, Recently, a novel mammalian protein kinase (p38) that shares sequence similarity with mitogen-activated protein (MAP) kinases was identified, Here, we demonstrate that p38, like JNK, is activated by treatment of cells with pro-inflammatory cytokines and environmental stress, The mechanism of p38 activation is mediated by dual phosphorylation on Thr-180 and Tyr-182, Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells, Together, these data establish that p38 is a member of the mammalian MAP kinase group.