Bi-directional regulation of UV-induced activation of p38 kinase and c-Jun N-terminal kinase by G protein βγ-subunits

Abstract

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 βγ-subunit (Gβγ) mediates the UV-induced activation of p38 and JNK. Gβγ overexpression in COS-1 cells amplified the UV-induced activation of p38 but reduced JNK activation. The overexpression of the C-terminal region of β-adrenergic receptor kinase (βARKct) decreased the UV-induced activation of p38 but increased JNK activation. Gβ1γ2 expression increased MKK3/6 phosphorylation with a concomitant decrease in MKK4 phosphorylation, which contrasts with βARKct expression. Gβ1γ2 or βARKct 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 Gβγ was found to mediate about half of the UV-induced activation of p38, it was found that exogenous Gβγ mediates the bi-directional regulation of UV-induced p38 and JNK activation, and that this bidirectional regulation results from the inhibition of JNK activation by the p38 activated via Gβγ in the COS-1 cells.