Angiotensin II stimulates rapid serine phosphorylation of transcription factor Stat3.
In rat neonatal cardiac fibroblasts and CHO-K1 cells expressing angiotensin type 1 receptors, angiotensin II (AII) rapidly caused a time dependent reduction in the SDS-polyacrylamide gel electrophoretic mobility of Stat3 (Signal Transducer and Activator of Transcription). This was concentration dependent and detected at a low/physiological concentration of AII (1 nM), with initial effect observed as early as 2 min; and maximal at 5 min. The rapid stimulation of Stat3 mobility retardation by AII, paralleled the rapid activation of MAP kinases (mitogen-activated protein kinases), and both were sensitive to the MAP kinase kinase 1 inhibitor, PD98059. Immunoprecipitation of Stat3 from [32P] labeled cells demonstrated a 4-fold increase in Stat3 phosphorylation in response to AII, and phosphoamino acid analysis indicated that phosphorylation occurred on serine residues. Angiotensin II-induced rapid phosphorylation of Stat3 was also sensitive to the MAP kinase kinase 1 inhibitor, PD98059. Treatment of immunoprecipitated Stat3 from AII-treated cells with protein phosphatase- PP-2A, reversed the AII-induced retardation of Stat3 mobility. These results demonstrate that AII rapidly induces Stat3 serine phosphorylation through a MAP kinase kinase 1 dependent pathway. Rapid stimulation of Stat3 serine phosphorylation by AII may have implications in the modulation of its transcriptional activity and gene expression.
Bhat
G J
GJ
Weis Center for Research, Geisinger Clinic, Danville, PA 17822, USA.
Baker
K M
KM
D000803:Angiotensin I; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D016466:CHO Cells; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D007700:Kinetics; D020929:Mitogen-Activated Protein Kinase Kinases; D009206:Myocardium / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D051381:Rats; D011945:Receptors, Angiotensin / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor; D012694:Serine; D015534:Trans-Activators / Q000302:isolation & purification / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D047428:Protein Kinase Inhibitors; D011945:Receptors, Angiotensin; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; D000804:Angiotensin II; D012694:Serine; D000803:Angiotensin I; D020929:Mitogen-Activated Protein Kinase Kinases; D010749:Phosphoprotein Phosphatases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one