Misra-Press A, Rim C S, Yao H, Roberson M S, Stork P J
Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
J Biol Chem. 1995 Jun 16;270(24):14587-96. doi: 10.1074/jbc.270.24.14587.
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 vivo 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 and agents that induce cellular stress, suggesting that these MKPs may have distinct physiological functions.
丝裂原活化蛋白（MAP）激酶处于各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激酶的失活是通过特定的MAP激酶磷酸酶（MKP）进行去磷酸化介导的。据报道，一种MKP（MKP-1，也称为3CH134、Erp或CL100）在广泛的组织和细胞中表达。我们报告了从PC12细胞中分离出的第二种广泛表达的MKP，称为MKP-2的鉴定。MKP-2与MKP-1具有显著的同源性（氨基酸水平为58.8%），并且与MKP-1一样，在体外对MAP激酶表现出钒酸盐敏感的磷酸酶活性。体内过表达MKP-2可抑制PC12细胞中MAP激酶依赖性基因转录。MKP-2在组织分布以及生长因子和诱导细胞应激的试剂诱导的程度方面与MKP-1不同，这表明这些MKP可能具有不同的生理功能。
