beta 2-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 a ctivate c-Jun N-terminal kinase (JNK), a subfamily of mitogen-activated pro tein kinases (MAPKs), through Rho family small GTPases in mammalian cells. We investigated the signaling pathway linking the Gs-coupled beta2-adrenerg ic receptor with JNK, using smooth muscle DDT1 MF-2 cells, which natively e xpress the beta2-adrenergic receptor. Stimulation of the beta2-adrenergic r eceptor activated JNK in a time-dependent manner, and a cell-permeable cycl ic adenosine monophosphate analogue (8-Br-cAMP) activated JNK. The beta2-ad renergic receptor- or 8-Br-cAMP-induced activation of JNK required Rho fami ly small GTPases. Also, the beta2-adrenergic receptor or 8-Br-cAMP induced activation of Rho family small GTPases. These results demonstrate that the pa-adrenergic receptor/cAMP leads to JNK activation through Rho family smal l GTPases in DDT1 MF-2 cells. Activation of Rho family small GTPases may pr ovide a common step in GPCR-mediated JNK activation. (C) 2001 Academic Pres s.