Sever R, Turner R
MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Biochem Biophys Res Commun. 1996 Nov 12;228(2):259-66. doi: 10.1006/bbrc.1996.1650.
The AP-1 transcription factor family is subject to sophisticated regulation in response to cell growth and stress stimuli. We show here that the transcriptional activity of c-Jun, a key AP-1 component, is stimulated by overexpression of the c-Mos proto-oncogene product in mammalian cells. This stimulation requires serines 63 and 73 of c-Jun, indicating that it is likely to be mediated by proline-directed kinase(s). Co-transfection of MKP-1, a specific MAP kinase antagonist, blocks the stimulation of c-Jun by c-Mos, while co-transfection of a dominant negative form of c-Raf-1 does not. Conditioned medium from c-Mos transfected cells fails to activate c-Jun in recipient cells, arguing against the involvement of a diffusible mitogen. These data suggest that c-Mos exerts its effect on c-Jun directly through a MAP kinase, acting downstream of c-Raf-1.
AP-1转录因子家族在响应细胞生长和应激刺激时受到复杂的调控。我们在此表明，c-Jun（一种关键的AP-1成分）的转录活性在哺乳动物细胞中被c-Mos原癌基因产物的过表达所刺激。这种刺激需要c-Jun的丝氨酸63和73，表明它可能由脯氨酸定向激酶介导。特异性丝裂原活化蛋白激酶（MAP激酶）拮抗剂MKP-1的共转染可阻断c-Mos对c-Jun的刺激，而c-Raf-1的显性负性形式的共转染则不能。来自c-Mos转染细胞的条件培养基无法激活受体细胞中的c-Jun，这排除了可扩散有丝分裂原的参与。这些数据表明，c-Mos通过MAP激酶直接对c-Jun发挥作用，作用于c-Raf-1的下游。
