PMID- 11978790 OWN - NLM STAT- MEDLINE DCOM- 20020827 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 277 IP - 27 DP - 2002 Jul 5 TI - Bi-directional regulation of UV-induced activation of p38 kinase and c-Jun N-terminal kinase by G protein beta gamma-subunits. PG - 24197-203 AB - Ultraviolet (UV) irradiation induces various cellular responses by activating many UV-responsive enzymes including mitogen-activated protein kinases (MAPKs). Various G protein-coupled receptor agonists also activate MAPKs, but it is not known whether or not G proteins also mediate the UV-induced activation of MAPKs. Therefore, this study was undertaken to determine whether the G protein betagamma-subunit (Gbetagamma) mediates the UV-induced activation of p38 and JNK. Gbetagamma overexpression in COS-1 cells amplified the UV-induced activation of p38 but reduced JNK activation. The overexpression of the C-terminal region of beta-adrenergic receptor kinase (betaARKct) decreased the UV-induced activation of p38 but increased JNK activation. Gbeta(1)gamma(2) expression increased MKK3/6 phosphorylation with a concomitant decrease in MKK4 phosphorylation, which contrasts with betaARKct expression. Gbeta(1)gamma(2) or betaARKct expression resulted in corresponding changes in the transcriptional activity of CHOP and c-Jun. Treatment with a p38 inhibitor, SB203580, or the expression of a kinase-inactive p38 increased the UV-induced JNK activation. Expression of the constitutively active MKK6 decreased the UV-induced JNK activation. In summary, although the endogenous Gbetagamma was found to mediate about half of the UV-induced activation of p38, it was found that exogenous Gbetagamma mediates the bi-directional regulation of UV-induced p38 and JNK activation, and that this bi-directional regulation results from the inhibition of JNK activation by the p38 activated via Gbetagamma in the COS-1 cells. FAU - Seo, MiRan AU - Seo M AD - Department of Biochemistry and Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Korea. FAU - Lee, Yun-Il AU - Lee YI FAU - Cho, Chin-Ho AU - Cho CH FAU - Bae, Chang-Dae AU - Bae CD FAU - Kim, In-Hoo AU - Kim IH FAU - Juhnn, Yong-Sung AU - Juhnn YS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20020426 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (G-protein Beta gamma) RN - 0 (GTP-Binding Protein beta Subunits) RN - 0 (GTP-Binding Protein gamma Subunits) RN - 0 (Recombinant Proteins) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.6.5.1 (Heterotrimeric GTP-Binding Proteins) SB - IM MH - Animals MH - Cell Line MH - Chlorocebus aethiops MH - Cloning, Molecular MH - Enzyme Activation MH - *GTP-Binding Protein beta Subunits MH - *GTP-Binding Protein gamma Subunits MH - Heterotrimeric GTP-Binding Proteins/chemistry/metabolism MH - JNK Mitogen-Activated Protein Kinases MH - Kidney MH - Mitogen-Activated Protein Kinases/metabolism/*radiation effects MH - Recombinant Proteins/metabolism MH - *Ultraviolet Rays MH - p38 Mitogen-Activated Protein Kinases EDAT- 2002/04/30 10:00 MHDA- 2002/08/28 10:01 CRDT- 2002/04/30 10:00 PHST- 2002/04/30 10:00 [pubmed] PHST- 2002/08/28 10:01 [medline] PHST- 2002/04/30 10:00 [entrez] AID - S0021-9258(19)66587-7 [pii] AID - 10.1074/jbc.M201717200 [doi] PST - ppublish SO - J Biol Chem. 2002 Jul 5;277(27):24197-203. doi: 10.1074/jbc.M201717200. Epub 2002 Apr 26.