RRC ID 2040
Author Arai K, Maruyama Y, Nishida M, Tanabe S, Takagahara S, Kozasa T, Mori Y, Nagao T, Kurose H.
Title Differential requirement of G alpha12, G alpha13, G alphaq, and G beta gamma for endothelin-1-induced c-Jun NH2-terminal kinase and extracellular signal-regulated kinase activation.
Journal Mol Pharmacol
Abstract In the present study, we examined the roles of G(12), G(13), G(q), and G(i) in endothelin-1-induced hypertrophic responses. Endothelin-1 stimulation activated extracellular signal-regulated kinase (ERK) and c-Jun NH(2)-terminal kinase (JNK) in cultured rat neonatal myocytes. The activation of JNK, but not ERK, was inhibited by the expression of carboxyl terminal regions of G alpha(12) and G alpha(13). JNK activation was also inhibited by expression of the G alpha(12)/G alpha(13)-specific inhibitor regulator of G protein signaling (RGS) domain of p115RhoGEF and the G alpha(q)-specific inhibitor RGS domain of the G protein-coupled receptor kinase 2 (GRK2-RGS). JNK activation was not, however, inhibited by expression of the carboxyl terminal region of G protein-coupled receptor kinase 2 (GRK2-ct), which is a G beta gamma-sequestering polypeptide. Additionally, JNK activation but not ERK activation was inhibited by the expression of C3 exoenzyme that inactivates small GTPase Rho. These results suggest that JNK activation by G alpha(12), G alpha(13), and G alpha(q) is involved in Rho. On the other hand, ERK activation was inhibited by pertussis toxin treatment, the receptor-G(i) uncoupler, and GRK2-ct. Thus, ERK was activated by G alpha(i)- and G beta gamma-dependent pathways. These results clearly demonstrate that differential pathways activate JNK and ERK.
Volume 63(3)
Pages 478-88
Published 2003-3-1
DOI 10.1124/mol.63.3.478
PMID 12606754
MeSH Animals CHO Cells Cells, Cultured Cricetinae DNA-Binding Proteins / metabolism* Endothelin-1 / metabolism* Enzyme Activation GTP-Binding Protein alpha Subunits, G12-G13 GTP-Binding Protein alpha Subunits, Gq-G11 GTP-Binding Protein beta Subunits* GTP-Binding Protein gamma Subunits* Heterotrimeric GTP-Binding Proteins / metabolism* JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases / metabolism* Monocytes / enzymology Monocytes / metabolism* Rats Rats, Sprague-Dawley
IF 3.664
Times Cited 65
DNA material AxCALacZ (RDB01745)