G alpha q-dependent activation of mitogen-activated protein kinase kinase 4/c-Jun N-terminal kinase cascade

G-protein-coupled receptors (GPCRs) typically activate c-Jun N-terminal kin ase (JNK) through the G protein beta gamma subunit (G beta gamma), in a man ner dependent on Rho family small GTPases, in mammalian cells. Here we show that JNK activation by the prototypic Gp-coupled alpha 1B-adrenergic recep tor is mediated by the a subunit of Gq (G alphaq), not by G beta gamma, usi ng a transient transfection system in human embryonic kidney cells. JNK act ivation by the alpha 1B-adrenergic receptor/G alphaq was selectively mediat ed by mitogen-activated protein kinase kinase 4 (MKK4), but not MKK7. Also, MKK4 activation by the alpha 1B-adrenergic receptor/G alphaq required c-Sr c and Rho family small GTPases. Furthermore, activation of the alpha 1B-adr energic receptor stimulated JNK activity through Src family tyrosine kinase s and Rho family small GTPases in hamster smooth muscle cells that natively express the alpha 1B-adrenergic receptor. Together, these results suggest that the alpha 1B-adrenergic receptor/G alphaq may up-regulate JNK activity through a MKK4 pathway dependent on c-Src and Rho family small GTPases in mammalian cells. (C) 2001 Academic Press.