Beta2-adrenergic receptor/cyclic adenosine monophosphate (cAMP) leads to JNK activation through Rho family small GTPases.
Gi- and Gq-coupled G protein-coupled receptors (GPCRs) have been shown to activate c-Jun N-terminal kinase (JNK), a subfamily of mitogen-activated protein kinases (MAPKs), through Rho family small GTPases in mammalian cells. We investigated the signaling pathway linking the Gs-coupled beta2-adrenergic receptor with JNK, using smooth muscle DDT1 MF-2 cells, which natively express the beta2-adrenergic receptor. Stimulation of the beta2-adrenergic receptor activated JNK in a time-dependent manner, and a cell-permeable cyclic adenosine monophosphate analogue (8-Br-cAMP) activated JNK. The beta2-adrenergic receptor- or 8-Br-cAMP-induced activation of JNK required Rho family small GTPases. Also, the beta2-adrenergic receptor or 8-Br-cAMP induced activation of Rho family small GTPases. These results demonstrate that the beta2-adrenergic receptor/cAMP leads to JNK activation through Rho family small GTPases in DDT1 MF-2 cells. Activation of Rho family small GTPases may provide a common step in GPCR-mediated JNK activation.
Yamauchi
J
J
Department of Molecular Cell Pharmacology, National Children's Medical Research Center, 3-35-31 Taishido, Tokyo, Setagaya-ku, 154-8509, Japan.
Hirasawa
A
A
Miyamoto
Y
Y
Itoh
H
H
Tsujimoto
G
G
D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D000242:Cyclic AMP / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D018343:Receptors, Adrenergic, beta-2; D000242:Cyclic AMP; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020741:rho GTP-Binding Proteins