ANGIOTENSIN-II INDUCES 3CH134, A PROTEIN-TYROSINE-PHOSPHATASE, IN VASCULAR SMOOTH-MUSCLE CELLS

Angiotensin II is a potent growth factor for vascular smooth muscle ce lls and shares many signal transduction mechanisms with mitogens, incl uding stimulation of mitogen-activated protein (MAP) kinases and prote in tyrosine phosphorylation. Regulation of tyrosine phosphorylation in volves both protein-tyrosine kinases and protein-tyrosine phosphatases (PTPases). To investigate the role of PTPases in angiotensin II-media ted events, we studied the expression of a transcriptionally regulated PTPase, 3CH134, which has selective activity toward MAP kinase. Angio tensin II rapidly induced 3CH134 mRNA (30 min maximum) in a concentrat ion-dependent manner (100 nM maximum). Platelet-derived growth factor, alpha-thrombin, hydrogen peroxide, phorbol 12-myristate 13-acetate, a nd ionomycin also induced 3CH134 but to levels lower than angiotensin H. Induction of 3CH134 by angiotensin II was partially inhibited after down-regulating protein kinase C but was fully inhibited after chelat ing intracellular Ca2+. Treatment with both phorbol 12-myristate 13-ac etate and ionomycin induced 3CH134 mRNA to levels seen with angiotensi n II, indicating that Ca2+ mobilization and protein kinase C activatio n can act synergistically to induce 3CH134. Angiotensin II stimulated 3CH134 protein synthesis after 1 h as measured by immunoprecipitation of 3CH134 from [S-35]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 ro le for PTPases in regulating angiotensin II-stimulated events mediated by MAP kinases and tyrosine kinases.