Evidence for the involvement of Gi2 in activation of extracellular signal-regulated kinases in hepatocytes.
BACKGROUND
Activation of the extracellular signal-regulated kinases ERK1 and ERK2 in hepatocytes by prostaglandin (PG)F2alpha was recently found to be inhibited by pertussis toxin (PTX) suggesting a role for Gi proteins.


RESULTS
Targeting the Gi2alpha expression by a specific ribozyme inhibited the PGF2alpha -induced ERK1/2 activation in hepatocytes. On the other hand a non-cleaving form of the Gi2alpha ribozyme did not significantly decrease the ERK1/2 activation. In ribozyme-treated cells the Gi2alpha protein level was reduced, while the Gqalpha level was not affected thus confirming the specificity of the ribozyme.


CONCLUSIONS
The present data suggest an important role of Gi2 in PGF2alpha -induced ERK1/2 signaling in hepatocytes.
Melien
O
O
Department of Pharmacology, Faculty of Medicine, University of Oslo, Box 1057 Blindern, N-0316, Oslo, Norway. oyvind.melien@c2i.net
Christoffersen
T
T
Sioud
M
M
D000818:Animals; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D016337:RNA, Catalytic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D016337:RNA, Catalytic; D015237:Dinoprost; D037342:Pertussis Toxin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C498017:Gnai2 protein, rat