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Research ArticleArticle

Differential Requirement of Gα12, Gα13, Gαq, and Gβγ for Endothelin-1-Induced c-Jun NH2-Terminal Kinase and Extracellular Signal-Regulated Kinase Activation

Ken Arai, Yoshiko Maruyama, Motohiro Nishida, Shihori Tanabe, Shuichi Takagahara, Tohru Kozasa, Yasuo Mori, Taku Nagao and Hitoshi Kurose
Molecular Pharmacology March 2003, 63 (3) 478-488; DOI: https://doi.org/10.1124/mol.63.3.478
Ken Arai
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Yoshiko Maruyama
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Motohiro Nishida
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Shihori Tanabe
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Shuichi Takagahara
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Tohru Kozasa
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Yasuo Mori
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Taku Nagao
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Hitoshi Kurose
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Abstract

In the present study, we examined the roles of G12, G13, Gq, and Gi in endothelin-1-induced hypertrophic responses. Endothelin-1 stimulation activated extracellular signal-regulated kinase (ERK) and c-Jun NH2-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 Gα12 and Gα13. JNK activation was also inhibited by expression of the Gα12/Gα13-specific inhibitor regulator of G protein signaling (RGS) domain of p115RhoGEF and the Gαq-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 Gβγ-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 Gα12, Gα13, and Gαq is involved in Rho. On the other hand, ERK activation was inhibited by pertussis toxin treatment, the receptor-Gi uncoupler, and GRK2-ct. Thus, ERK was activated by Gαi- and Gβγ-dependent pathways. These results clearly demonstrate that differential pathways activate JNK and ERK.

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Molecular Pharmacology: 63 (3)
Molecular Pharmacology
Vol. 63, Issue 3
1 Mar 2003
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Research ArticleArticle

Differential Requirement of Gα12, Gα13, Gαq, and Gβγ for Endothelin-1-Induced c-Jun NH2-Terminal Kinase and Extracellular Signal-Regulated Kinase Activation

Ken Arai, Yoshiko Maruyama, Motohiro Nishida, Shihori Tanabe, Shuichi Takagahara, Tohru Kozasa, Yasuo Mori, Taku Nagao and Hitoshi Kurose
Molecular Pharmacology March 1, 2003, 63 (3) 478-488; DOI: https://doi.org/10.1124/mol.63.3.478

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Research ArticleArticle

Differential Requirement of Gα12, Gα13, Gαq, and Gβγ for Endothelin-1-Induced c-Jun NH2-Terminal Kinase and Extracellular Signal-Regulated Kinase Activation

Ken Arai, Yoshiko Maruyama, Motohiro Nishida, Shihori Tanabe, Shuichi Takagahara, Tohru Kozasa, Yasuo Mori, Taku Nagao and Hitoshi Kurose
Molecular Pharmacology March 1, 2003, 63 (3) 478-488; DOI: https://doi.org/10.1124/mol.63.3.478
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