Bi-directional regulation of UV-induced activation of p38 kinase and c-Jun N-terminal kinase by G protein beta gamma-subunits.
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.
Seo
MiRan
M
Department of Biochemistry and Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.
Lee
Yun-Il
YI
Cho
Chin-Ho
CH
Bae
Chang-Dae
CD
Kim
In-Hoo
IH
Juhnn
Yong-Sung
YS
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D004789:Enzyme Activation; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D007668:Kidney; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000528:radiation effects*; D011994:Recombinant Proteins / Q000378:metabolism; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases
C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D011994:Recombinant Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020962:Heterotrimeric GTP-Binding Proteins