AVP-induced activation of MAP kinase in vascular smooth muscle cells is mediated through protein kinase C

A. Kribben, E. D. Wieder, X. Li, V. Van Putten, Y. Granot, R. W. Schrier, R. A. Nemenoff

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Arginine vasopressin (AVP) has been shown to stimulate tyrosine phosphorylation and activation of p42 mitogen-activated protein (MAP) kinase (p42MAPK) in vascular smooth muscle cells (VSMC). In VSMC, AVP increases free intracellular Ca2+ concentration ([Ca2+](i)) and activates protein kinase C (PKC) through activation of phospholipase C. The contribution of PKC and [Ca2+](i) in p42MAPK regulation was therefore determined. Activation of PKC by phorbol 12-myristate 13-acetate (PMA) stimulated tyrosine phosphorylation and activation of p42MAPK to the same extent as AVP. Inhibition of PKC by staurosporine or downregulation of PKC by PMA pretreatment abolished AVP- induced stimulation of p42MAPK. When [Ca2+](i) was elevated to the same level as with AVP, using either ionomycin (0.1 μM) or thapsigargin (0.1 μM), MAP kinase was only partially activated. Elevation of [Ca2+](i) to supraphysiological levels by 1 μM ionomycin stimulated MAP kinase activity to the same extent as AVP. This effect was blocked by downregulation of PKC. The intracellular Ca2+ chelator BAPTA [1,2-bis(2-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid] blocked AVP-induced [Ca2+](i) increase but did not affect AVP stimulation of p42MAPK. Thus AVP-induced activation of p42MAPK requires only the activation of PKC but not an increase in [Ca2+](i).

Original languageEnglish (US)
Pages (from-to)C939-C945
JournalAmerican Journal of Physiology - Cell Physiology
Volume265
Issue number4 34-4
DOIs
StatePublished - 1993

Keywords

  • arginine vasopressin
  • intracellular calcium
  • p42 mitogen-activated protein kinase

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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