title: The c-Mos proto-oncogene product stimulates c-Jun transcriptional activity by a MAP kinase-dependent mechanism.
abstract: 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.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Sever
authors.forename: R
authors.initials: R
authors.lastname: Turner
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D017930:Genes, Reporter; D016758:Genes, jun; D007739:L Cells; D008322:Mammals; D051379:Mice; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D017231:Proto-Oncogene Proteins c-mos / Q000378:metabolism*; D011519:Proto-Oncogenes; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012694:Serine; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D012694:Serine; D015500:Chloramphenicol O-Acetyltransferase; D017231:Proto-Oncogene Proteins c-mos; D017871:Calcium-Calmodulin-Dependent Protein Kinases