PMID- 10050039 OWN - NLM STAT- MEDLINE DCOM- 19990625 LR - 20190513 IS - 0021-924X (Print) IS - 0021-924X (Linking) VI - 125 IP - 3 DP - 1999 Mar TI - Activation of c-fos promoter by Gbetagamma-mediated signaling: involvement of Rho and c-Jun N-terminal kinase. PG - 515-21 AB - Several extracellular stimuli mediated by G protein-coupled receptors activate c-fos promoter. Recently, we and other groups have demonstrated that signals from G protein-coupled receptors stimulate mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. The activation of these three MAPKs is mediated in part by the G protein betagamma subunit (Gbetagamma). In this study, we characterized the signals from Gbetagamma to c-fos promoter using transient transfection of c-fos luciferase into human embryonal kidney 293 cells. Activation of m2 muscarinic acetylcholine receptor and overexpression of Gbetagamma, but not constitutively active Galphai2, stimulated c-fos promoter activity. The c-fos promoter activation by m2 receptor and Gbetagamma was inhibited by beta-adrenergic receptor kinase C-terminal peptide (betaARKct), which functions as a Gbetagamma antagonist. MEK1 inhibitor PD98059 and kinase-deficient mutant of JNK kinase, but not p38 MAPK inhibitor SB203580, attenuated the m2 receptor- and Gbetagamma-induced c-fos promoter activation. Activated mutants of Ras and Rho stimulated the c-fos promoter activity, and the dominant negative mutants of Ras and Rho inhibited the c-fos promoter activation by m2 receptor and Gbetagamma. Moreover, c-fos promoter activation by m2 receptor, Gbetagamma, and active Rho, but not active Ras, was inhibited by botulinum C3 toxin. These data indicated that both Ras- and Rho-dependent signaling pathways are essential for c-fos promoter activation mediated by Gbetagamma. FAU - Sun, Y AU - Sun Y AD - Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama, 226-8501, Japan. FAU - Yamauchi, J AU - Yamauchi J FAU - Kaziro, Y AU - Kaziro Y FAU - Itoh, H AU - Itoh H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Biochem JT - Journal of biochemistry JID - 0376600 RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.12.2 (MAP Kinase Kinase 4) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM MH - Calcium-Calmodulin-Dependent Protein Kinases/*genetics MH - Cell Line MH - GTP-Binding Proteins/*genetics MH - Gene Expression Regulation MH - *Genes, fos MH - Humans MH - *JNK Mitogen-Activated Protein Kinases MH - MAP Kinase Kinase 4 MH - *Mitogen-Activated Protein Kinase Kinases MH - Promoter Regions, Genetic MH - Protein Kinases/*genetics MH - *Signal Transduction/genetics EDAT- 1999/03/02 00:00 MHDA- 1999/03/02 00:01 CRDT- 1999/03/02 00:00 PHST- 1999/03/02 00:00 [pubmed] PHST- 1999/03/02 00:01 [medline] PHST- 1999/03/02 00:00 [entrez] AID - 10.1093/oxfordjournals.jbchem.a022315 [doi] PST - ppublish SO - J Biochem. 1999 Mar;125(3):515-21. doi: 10.1093/oxfordjournals.jbchem.a022315.