Involvement of c-jun N-terminal kinase and p38 mitogen-activated protein kinase in alpha 1B-adrenergic receptor/G alpha q-induced inhibition of cell proliferation

Certain G protein-coupled receptors (GPCRs) stimulate the activities of c-J un N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), members of the MAPK family. We investigated the role of JNK and p38 MAPK a ctivation induced by the alpha 1B-adrenergic receptor in the proliferation of human embryonic kidney 293T cells. Activation of the alpha 1B-adrenergic receptor resulted in inhibition of cell proliferation. This receptor-induc ed inhibition of proliferation was blocked by a kinase-deficient MKK4 and b y the p38 MAPK inhibitor SB203580. Additionally, transfection of constituti vely activated G alphaq into cells also led to inhibition of proliferation in a JNK- and p38 MAPK-dependent manner. These results demonstrate that the alpha 1B-adrenergic receptor/G alphaq signaling inhibits cell proliferatio n through pathways involving JNK and p38 MAPK. (C) 2001 Academic Press.