MKP-1 (3CH134), AN IMMEDIATE-EARLY GENE-PRODUCT, IS A DUAL-SPECIFICITY PHOSPHATASE THAT DEPHOSPHORYLATES MAP KINASE IN-VIVO
MKP-1 (3CH134), AN IMMEDIATE-EARLY GENE-PRODUCT, IS A DUAL-SPECIFICITY PHOSPHATASE THAT DEPHOSPHORYLATES MAP KINASE IN-VIVO
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DOI：
10.1016/0092-8674(93)90383-2
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发表时间：
1993-11-05
期刊：
影响因子：
64.5
通讯作者：
TONKS, NK
中科院分区：
文献类型：
--
作者：
SUN, H;CHARLES, CH;TONKS, NK
细胞的促有丝分裂刺激诱导MAP激酶的快速和瞬时活化。在这里，我们报告的生长因子诱导基因，3CH 134，编码的双特异性磷酸酶，去磷酸化和失活p42 MAPK在体外和体内。在体外，3CH 134蛋白使p42 MAPK中的T183和Y185去磷酸化。在血清刺激的正常成纤维细胞中，p42 MAPK的失活动力学与新合成的3CH 134蛋白的出现相一致，并且蛋白合成抑制剂放线菌酮导致MAP激酶的持续激活。COS细胞中3CH 134的表达导致磷酸酪氨酸蛋白质谱中p42 MAPK的选择性去磷酸化。3CH 134阻断由血清、致癌Ras或活化的Raf介导的p42 MAPK的磷酸化和活化，而磷酸酶的催化失活突变体Cys-258->Ser在类似条件下增强MAP激酶磷酸化。突变体3CH 134蛋白还与磷酸化形式的p42 MAPK形成物理复合物。这些研究结果表明，3CH 134是一种生理MAP激酶磷酸酶，我们建议这种磷酸酶的名称MKP-1。
Mitogenic stimulation of cells induces rapid and transient activation of MAP kinases. Here we report that a growth factor-inducible gene, 3CH134, encodes a dual specificity phosphatase that dephosphorylates and inactivates p42MAPK both in vitro and in vivo. In vitro, 3CH134 protein dephosphorylates both T183 and Y185 in p42MAPK. In serum-stimulated normal fibroblasts, the kinetics of inactivation of p42MAPK coincides with the appearance of newly synthesized 3CH134 protein, and the protein synthesis inhibitor cycloheximide leads to persistent activation of MAP kinase. Expression of 3CH134 in COS cells leads to selective dephosphorylation of p42MAPK from the spectrum of phosphotyrosyl proteins. 3CH134 blocks phosphorylation and activation of p42MAPK Mediated by serum, oncogenic Ras, or activated Raf, whereas the catalytically inactive mutant of the phosphatase, Cys-258-->Ser, augments MAP kinase phosphorylation under similar conditions. The mutant 3CH134 protein also forms a physical complex with the phosphorylated form of p42MAPK. These findings suggest that 3CH134 is a physiological MAP kinase phosphatase; we propose the name MKP-1 for this phosphatase.