Minden A, Lin A, Smeal T, Dérijard B, Cobb M, Davis R, Karin M
Department of Pharmacology, University of California, San Diego School of Medicine, La Jolla 92093-0636.
Mol Cell Biol. 1994 Oct;14(10):6683-8. doi: 10.1128/mcb.14.10.6683-6688.1994.
c-Jun transcriptional activity is stimulated by phosphorylation at two N-terminal sites: Ser-63 and -73. Phosphorylation of these sites is enhanced in response to a variety of extracellular stimuli, including growth factors, cytokines, and UV irradiation. New members of the mitogen-activated protein (MAP) kinase group of signal-transducing enzymes, termed JNKs, bind to the activation domain of c-Jun and specifically phosphorylate these sites. However, the N-terminal sites of c-Jun were also suggested to be phosphorylated by two other MAP kinases, ERK1 and ERK2. Despite these reports, we find that unlike the JNKs, ERK1 and ERK2 do not phosphorylate the N-terminal sites of c-Jun in vitro; instead they phosphorylate an inhibitory C-terminal site. Furthermore, the phosphorylation of c-Jun in vivo at the N-terminal sites correlates with activation of the JNKs but not the ERKs. The ERKs are probably involved in the induction of c-fos expression and thereby contribute to the stimulation of AP-1 activity. Our study suggests that two different branches of the MAP kinase group are involved in the stimulation of AP-1 activity through two different mechanisms.
c-Jun的转录活性受两个N端位点（Ser-63和-73）磷酸化的刺激。响应多种细胞外刺激，包括生长因子、细胞因子和紫外线照射，这些位点的磷酸化会增强。信号转导酶促分裂原活化蛋白（MAP）激酶组的新成员，称为JNKs，与c-Jun的活化结构域结合并特异性磷酸化这些位点。然而，c-Jun的N端位点也被认为可被另外两种MAP激酶ERK1和ERK2磷酸化。尽管有这些报道，但我们发现，与JNKs不同，ERK1和ERK2在体外不会磷酸化c-Jun的N端位点；相反，它们会磷酸化一个抑制性C端位点。此外，c-Jun在体内N端位点的磷酸化与JNKs的激活相关，而与ERK的激活无关。ERK可能参与c-fos表达的诱导，从而促进AP-1活性的刺激。我们的研究表明，MAP激酶组的两个不同分支通过两种不同机制参与AP-1活性的刺激。
