Involvement of c-Jun N-Terminal Kinase and p38 Mitogen-Activated Protein Kinase in α1B-Adrenergic Receptor/Gαq-Induced Inhibition of Cell Proliferation

Abstract

Certain G protein-coupled receptors (GPCRs) stimulate the activities of c-Jun 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 activation induced by the α1B-adrenergic receptor in the proliferation of human embryonic kidney 293T cells. Activation of the α1B-adrenergic receptor resulted in inhibition of cell proliferation. This receptor-induced inhibition of proliferation was blocked by a kinase-deficient MKK4 and by the p38 MAPK inhibitor SB203580. Additionally, transfection of constitutively activated Gαq into cells also led to inhibition of proliferation in a JNK- and p38 MAPK-dependent manner. These results demonstrate that the α1B-adrenergic receptor/Gαq signaling inhibits cell proliferation through pathways involving JNK and p38 MAPK.