The c-Mos proto-oncogene product stimulates c-Jun transcriptional activity by a MAP kinase-dependent mechanism.

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.