β2-Adrenergic Receptor/Cyclic Adenosine Monophosphate (cAMP) Leads to JNK Activation through Rho Family Small GTPases

Abstract

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 β2-adrenergic receptor with JNK, using smooth muscle DDT1 MF-2 cells, which natively express the β2-adrenergic receptor. Stimulation of the β2-adrenergic receptor activated JNK in a time-dependent manner, and a cell-permeable cyclic adenosine monophosphate analogue (8-Br-cAMP) activated JNK. The β2-adrenergic receptor- or 8-Br-cAMP-induced activation of JNK required Rho family small GTPases. Also, the β2-adrenergic receptor or 8-Br-cAMP induced activation of Rho family small GTPases. These results demonstrate that the β2-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.