Abe M K, Kuo W L, Hershenson M B, Rosner M R
Department of Pediatrics, University of Chicago, Chicago, Illinois 60637, USA.
Mol Cell Biol. 1999 Feb;19(2):1301-12. doi: 10.1128/MCB.19.2.1301.
Mitogen-activated protein (MAP) kinases play distinct roles in a variety of cellular signaling pathways and are regulated through multiple mechanisms. In this study, a novel 61-kDa member of the MAP kinase family, termed extracellular signal-regulated kinase 7 (ERK7), has been cloned and characterized. Although it has the signature TEY activation motif of ERK1 and ERK2, ERK7 is not activated by extracellular stimuli that typically activate ERK1 and ERK2 or by common activators of c-Jun N-terminal kinase (JNK) and p38 kinase. Instead, ERK7 has appreciable constitutive activity in serum-starved cells that is dependent on the presence of its C-terminal domain. Interestingly, the C-terminal tail, not the kinase domain, of ERK7 regulates its nuclear localization and inhibition of growth. Taken together, these results elucidate a novel type of MAP kinase whereby interactions via its C-terminal tail, rather than extracellular signal-mediated activation cascades, regulate its activity, localization, and function.
丝裂原活化蛋白（MAP）激酶在多种细胞信号通路中发挥着不同的作用，并通过多种机制进行调节。在本研究中，已克隆并鉴定出一种新型的61 kDa MAP激酶家族成员，称为细胞外信号调节激酶7（ERK7）。尽管ERK7具有ERK1和ERK2的标志性TEY激活基序，但它不会被通常激活ERK1和ERK2的细胞外刺激或c-Jun N端激酶（JNK）和p38激酶的常见激活剂所激活。相反，ERK7在血清饥饿细胞中具有明显的组成性活性，这种活性依赖于其C末端结构域的存在。有趣的是，ERK7的C末端尾巴而非激酶结构域调节其核定位和生长抑制。综上所述，这些结果阐明了一种新型的MAP激酶，即通过其C末端尾巴的相互作用而非细胞外信号介导的激活级联反应来调节其活性、定位和功能。
