Inhibition of platelet-derived growth factor receptor tyrosine kinase by atrial natriuretic peptide

Midori Awazu

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Atrial natriuretic peptide (ANP) is known to suppress platelet-derived growth factor (PDGF)-stimulated proliferation of rat cultured vascular smooth muscle cells. The present study examined whether ANP inhibits the PDGF receptor (PDGFR) tyrosine kinase activation, an initial event for PDGF cellular signaling. ANP reduced the in vive tyrosine phosphorylation of PDGFR stimulated by PDGF in a dose-dependent manner. This effect was not due to the reduction in PDGFR protein as detected by immunoblot analysis. 8-Bromocyclic GMP, a membrane- permeable 3',5'-cyclic monophosphate (cGMP) derivative, mimicked the action of ANP. HS-142-1, an antagonist for guanylate cyclase A (GC-A) and B, co-incubated with ANP, restored the PDGFinduced PDGFR autophosphotylation. The effect of ANP was also observed in the presence of a protein tyrosine phosphatase inhibitor, sodium orthovanadate. To confirm that ANP exerts its action by inhibiting protein tyrosine kinase (PTK), an in vitro kinase assay was performed. Cyclic GMP inhibited PTK activity of PDGFR partially purified by lectin affinity chromatography. In contrast, PTK activity in immobilized PDGFR immunocomplexes was not inhibited by cGMP. However, exogenous cGMP dependent protein kinase (PKG) reduced the PTK activity in the presence of cGMP. These results demonstrate that ANP suppresses PDGFR PTK through GC-A probably by activating PKG. This may be an important mechanism by which ANP exerts its anti-proliferative action antagonizing PDGF.

Original languageEnglish
Pages (from-to)356-362
Number of pages7
JournalKidney international
Volume52
Issue number2
DOIs
Publication statusPublished - 1997 Jan 1

Keywords

  • Atherosclerosis
  • Atrial natri-uretic peptide
  • Growth factor
  • Hypertension
  • Platelet-derived growth factor
  • Tyrosine kinase

ASJC Scopus subject areas

  • Nephrology

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