Angiotensin II stimulates phosphorylation of 4E-binding protein 1 and p70 S6 kinase in cultured vascular smooth muscle cells

Acta Pharmacol Sin. 2004 May;25(5):593-6.

Abstract

Aim: To examine the regulatory effects of angiotensin II (Ang II) on the phosphorylation of 4E-binding protein 1 (4E-BP1) and p70 S6 kinase in cultured vascular smooth muscle cells (VSMC), and the contribution of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) signaling pathway in this process.

Methods: VSMC obtained from rat thoracic aortas were cultured. The phosphorylation of 4E-BP1 and p70 S6 kinase was detected by immunoblotting.

Results: Ang II significantly increased the phosphorylation of 4E-BP1 and p70 S6 kinase, with the peaks occurring at, respectively, 10 min and 30 min, after stimulation with Ang II. The stimulatory effect of Ang II on 4E-BP1 and p70 S6 kinase phosphorylation was abrogated by Ang II type 1 receptor (A(T1) receptor) antagonist losartan, and suppressed by PI3K inhibitor LY294002 in a concentration-dependent manner.

Conclusion: Ang II treatment of VSMC induces the phosphorylation of 4E-BP1 and p70 S6 kinase via A(T1) receptor, and PI3K signaling pathway is involved in this process.

MeSH terms

  • Angiotensin II / pharmacology*
  • Angiotensin II Type 1 Receptor Blockers
  • Animals
  • Aorta, Thoracic / cytology
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Chromones / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • Losartan / pharmacology
  • Morpholines / pharmacology
  • Muscle, Smooth, Vascular / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
  • Signal Transduction

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Carrier Proteins
  • Chromones
  • Eif4ebp1 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphoproteins
  • Angiotensin II
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Ribosomal Protein S6 Kinases, 70-kDa
  • Losartan