A NOVEL MITOGEN-ACTIVATED PROTEIN-KINASE PHOSPHATASE - STRUCTURE, EXPRESSION, AND REGULATION
A NOVEL MITOGEN-ACTIVATED PROTEIN-KINASE PHOSPHATASE - STRUCTURE, EXPRESSION, AND REGULATION
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DOI：
10.1074/jbc.270.24.14587
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发表时间：
1995-06-16
影响因子：
4.8
通讯作者：
STORK, PJS
中科院分区：
文献类型：
--
作者：
MISRAPRESS, A;RIM, CS;STORK, PJS
丝裂原活化蛋白激酶是多种细胞外配体介导的信号通路的交汇点。它由双特异性激酶，MAP激酶激酶或MEK激活。MAP激酶失活是通过特异性MAP激酶磷酸酶（MKP）的去磷酸化介导的。据报道，一种MKP（MKP-1（也称为3CH 134、Erp或CL 100））在广泛的组织和细胞中表达。我们报告的第二个广泛表达的MKP，称为MKP-2，从PC 12细胞分离的鉴定。MKP-2显示出与MKP-1的显著同源性（在氨基酸水平上为58.8%），并且与MKP-1一样，在体外显示出对MAP激酶的钒酸盐敏感的磷酸酶活性。体内过表达MKP-2可抑制PC 12细胞MAP激酶依赖基因的转录。MKP-2与MKP-1的不同之处在于其组织分布和其受生长因子和诱导细胞应激的因子诱导的程度，这表明这些MKP可能具有不同的生理功能。
Mitogen-activated protein (MAP) kinase lies at the convergence of various extracellular ligand-mediated signaling pathways. It is activated by the dual-specificity kinase, MAP kinase kinase or MEK. MAP kinase inactivation is mediated by dephosphorylation via specific MAP kinase phosphatases (MKPs). One MKP (MKP-1 (also known as 3CH134, Erp, or CL100)) has been reported to be expressed in a wide range of tissues and cells. We report the identification of a second widely expressed MKP, termed MKP-2, isolated from PC12 cells. MKP-2 showed significant homology with MKP-1 (58.8% at the amino acid level) and, like MKP-1, displayed vanadate-sensitive phosphatase activity against MAP kinase in vitro. Overexpression of MKP-2 in vive inhibited MAP kinase-dependent gene transcription in PC12 cells. MKP-2 differed from MKP-1 in its tissue distribution and in its extent of induction by growth factors sind agents that induce cellular stress, suggesting that these MKPs may have distinct physiological functions.