Angiotensin II induces 3CH134, a protein-tyrosine phosphatase, in vascular smooth muscle cells.
Angiotensin II is a potent growth factor for vascular smooth muscle cells and shares many signal transduction mechanisms with mitogens, including stimulation of mitogen-activated protein (MAP) kinases and protein tyrosine phosphorylation. Regulation of tyrosine phosphorylation involves both protein-tyrosine kinases and protein-tyrosine phosphatases (PTPases). To investigate the role of PTPases in angiotensin II-mediated events, we studied the expression of a transcriptionally regulated PTPase, 3CH134, which has selective activity toward MAP kinase. Angiotensin II rapidly induced 3CH134 mRNA (30 min maximum) in a concentration-dependent manner (100 nM maximum). Platelet-derived growth factor, alpha-thrombin, hydrogen peroxide, phorbol 12-myristate 13-acetate, and ionomycin also induced 3CH134 but to levels lower than angiotensin II. Induction of 3CH134 by angiotensin II was partially inhibited after down-regulating protein kinase C but was fully inhibited after chelating intracellular Ca2+. Treatment with both phorbol 12-myristate 13-acetate and ionomycin induced 3CH134 mRNA to levels seen with angiotensin II, indicating that Ca2+ mobilization and protein kinase C activation can act synergistically to induce 3CH134. Angiotensin II stimulated 3CH134 protein synthesis after 1 h as measured by immunoprecipitation of 3CH134 from [35S]methionine-labeled cells using affinity-purified antibodies. These results establish 3CH134 as a dynamically regulated, immediate early gene in vascular smooth muscle cells and suggest a role for PTPases in regulating angiotensin II-stimulated events mediated by MAP kinases and tyrosine kinases.
Duff
J L
JL
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322.
Marrero
M B
MB
Paxton
W G
WG
Charles
C H
CH
Lau
L F
LF
Bernstein
K E
KE
Berk
B C
BC
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D054638:Dual Specificity Phosphatase 1; D004790:Enzyme Induction; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D010749:Phosphoprotein Phosphatases; D011493:Protein Kinase C / Q000378:metabolism; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D000804:Angiotensin II; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases