Involvement of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase in alpha1B-adrenergic receptor/Galphaq-induced inhibition of cell proliferation.
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 alpha1B-adrenergic receptor in the proliferation of human embryonic kidney 293T cells. Activation of the alpha1B-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 Galphaq into cells also led to inhibition of proliferation in a JNK- and p38 MAPK-dependent manner. These results demonstrate that the alpha1B-adrenergic receptor/Galphaq signaling inhibits cell proliferation through pathways involving JNK and p38 MAPK.
Yamauchi
J
J
Department of Molecular Cell Pharmacology, National Children's Medical Research Center, 3-35-31 Taishido, Setagaya-ku, Tokyo, 154-1809, Japan.
Itoh
H
H
Shinoura
H
H
Miyamoto
Y
Y
Hirasawa
A
A
Kaziro
Y
Y
Tsujimoto
G
G
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004274:DNA, Recombinant; D004791:Enzyme Inhibitors / Q000494:pharmacology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
D000316:Adrenergic alpha-Agonists; D002070:Butadienes; D004274:DNA, Recombinant; D004791:Enzyme Inhibitors; D007093:Imidazoles; D009570:Nitriles; D011725:Pyridines; D018340:Receptors, Adrenergic, alpha-1; C113580:U 0126; D010656:Phenylephrine; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins; C093642:SB 203580