Zhao M, New L, Kravchenko V V, Kato Y, Gram H, di Padova F, Olson E N, Ulevitch R J, Han J
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Mol Cell Biol. 1999 Jan;19(1):21-30. doi: 10.1128/MCB.19.1.21.
Members of the MEF2 family of transcription factors bind as homo- and heterodimers to the MEF2 site found in the promoter regions of numerous muscle-specific, growth- or stress-induced genes. We showed previously that the transactivation activity of MEF2C is stimulated by p38 mitogen-activated protein (MAP) kinase. In this study, we examined the potential role of the p38 MAP kinase pathway in regulating the other MEF2 family members. We found that MEF2A, but not MEF2B or MEF2D, is a substrate for p38. Among the four p38 group members, p38 is the most potent kinase for MEF2A. Threonines 312 and 319 within the transcription activation domain of MEF2A are the regulatory sites phosphorylated by p38. Phosphorylation of MEF2A in a MEF2A-MEF2D heterodimer enhances MEF2-dependent gene expression. These results demonstrate that the MAP kinase signaling pathway can discriminate between different MEF2 isoforms and can regulate MEF2-dependent genes through posttranslational activation of preexisting MEF2 protein.
转录因子MEF2家族的成员以同二聚体和异二聚体的形式与众多肌肉特异性、生长或应激诱导基因启动子区域中的MEF2位点结合。我们之前表明，p38丝裂原活化蛋白（MAP）激酶可刺激MEF2C的反式激活活性。在本研究中，我们研究了p38 MAP激酶途径在调节其他MEF2家族成员中的潜在作用。我们发现MEF2A是p38的底物，而MEF2B或MEF2D不是。在p38组的四个成员中，p38是MEF2A最有效的激酶。MEF2A转录激活域内的苏氨酸312和319是被p38磷酸化的调节位点。MEF2A-MEF2D异二聚体中MEF2A的磷酸化增强了MEF2依赖性基因表达。这些结果表明，MAP激酶信号通路可以区分不同的MEF2异构体，并可通过对已存在的MEF2蛋白进行翻译后激活来调节MEF2依赖性基因。
