Regulation of c-Jun N-terminal kinase by the ORL(1) receptor through multiple G proteins.
Nociceptin is an endogenous peptide that produces its biological effects by binding to the opioid receptor-like (ORL(1)) receptor. It has been shown that activation of ORL(1) receptor leads to inhibition of the adenylyl cyclase activity, but stimulation of the extracellular signal-regulated kinase and p38 subgroups of mitogen-activated protein kinases. In this report, we demonstrate that activation of the G protein-coupled ORL(1) receptor in transfected COS-7 cells leads to stimulation of the JNK subgroup of mitogen-activated protein kinases in a Ras/Rac-dependent manner, and it was insensitive to wortmannin. This increased JNK activity was mainly mediated by PTX-sensitive G(i) proteins, and partially contributed by a PTX-insensitive component. Among all known PTX-insensitive G proteins, G(z), G(12), G(14), and G(16) seemed to have functional coupling with the ORL(1) receptor in terms of JNK activation. Stimulation of the endogenous ORL(1) receptor in NG108-15 cells also led to activation of a PTX-sensitive JNK activity in a wortmannin-insensitive manner. The induced JNK activation is accompanied by the active phosphorylation of c-Jun and activating transcription factor-2. This is the first report that demonstrates the stimulatory effect of ORL(1) receptor on JNK, and the subsequent activation of c-Jun and activating transcription factor-2.
Chan
A S
AS
Department of Biochemistry and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Wong
Y H
YH
D037361:Adenylate Cyclase Toxin; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D020558:GTP Phosphohydrolases / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D020930:MAP Kinase Kinase Kinases / Q000502:physiology; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018847:Opioid Peptides / Q000494:pharmacology; D011957:Receptors, Opioid / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000077191:Wortmannin; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D037361:Adenylate Cyclase Toxin; D000730:Androstadienes; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020930:MAP Kinase Kinase Kinases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D018847:Opioid Peptides; D011957:Receptors, Opioid; D010566:Virulence Factors, Bordetella; D000077191:Wortmannin; D000094942:Nociceptin Receptor; D000097629:Nociceptin