Linkage between alpha(1) adrenergic receptor and the Jak/STAT signaling pathway in vascular smooth muscle cells.
The Jak/STAT pathway is activated following stimulation of the type I angiotensin II receptor. To examine whether this pathway is shared among other G-protein-coupled receptors, we studied the linkage between the alpha(1) adrenergic receptor and this pathway. The alpha(1) agonist phenylephrine induced tyrosine phosphorylation of Jak2, Tyk2, and STAT1 in vascular smooth muscle cells. The phosphorylation of Jak2 was prevented by the alpha(1) receptor antagonists prazosin and chloroethylclonidine, but not by WB4101, and that of STAT1 was inhibited by prazosin and the Jak2 inhibitor AG490. After stimulation with phenylephrine, Jak2 and STAT1 were found to associate with alpha(1B) receptor. Phenylephrine stimulated the DNA binding activity of STAT1. Protein synthesis promoted by phenylephrine was inhibited by prazosin, AG490, and the introduction of a decoy oligonucleotide for STAT1. These results suggested that alpha(1) receptor is linked to the Jak/STAT pathway and that this pathway mediates alpha(1) agonist-induced smooth muscle hypertrophy.
Sasaguri
T
T
Department of Bioscience, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan. sasaguri@ri.ncvc.go.jp
Teruya
H
H
Ishida
A
A
Abumiya
T
T
Ogata
J
J
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D010656:Phenylephrine / Q000494:pharmacology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D011518:Proto-Oncogene Proteins; D018340:Receptors, Adrenergic, alpha-1; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D010656:Phenylephrine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D053634:TYK2 Kinase; C070139:TYK2 protein, human