Angiotensin II induces 3CH134, a protein-tyrosine phosphatase, in vascular smooth muscle cells

J. L. Duff, M. B. Marrero, W. G. Paxton, C. H. Charles, L. F. Lau, K. E. Bernstein, B. C. Berk

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Abstract

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, α-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.

Original languageEnglish (US)
Pages (from-to)26037-26040
Number of pages4
JournalJournal of Biological Chemistry
Volume268
Issue number35
Publication statusPublished - Jan 1 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Angiotensin II induces 3CH134, a protein-tyrosine phosphatase, in vascular smooth muscle cells. / Duff, J. L.; Marrero, M. B.; Paxton, W. G.; Charles, C. H.; Lau, L. F.; Bernstein, K. E.; Berk, B. C.

In: Journal of Biological Chemistry, Vol. 268, No. 35, 01.01.1993, p. 26037-26040.

Research output: Contribution to journalArticle