Cellular growth inhibition by TGF-beta1 involves IRS proteins

FEBS Lett. 2004 May 7;565(1-3):117-21. doi: 10.1016/j.febslet.2004.03.082.

Abstract

In Mv1Lu cells, insulin partially reverses transforming growth factor-beta1 (TGF-beta1) growth inhibition in the presence of alpha5beta1 integrin antagonists. TGF-beta1 appears to induce phosphorylation of IRS-2 in these cells; this is inhibited by a TGF-beta antagonist known to reverse TGF-beta growth inhibition. Stable transfection of 32D myeloid cells (which lack endogenous IRS proteins and are insensitive to growth inhibition by TGF-beta1) with IRS-1 or IRS-2 cDNA confers sensitivity to growth inhibition by TGF-beta1; this IRS-mediated growth inhibition can be partially reversed by insulin in 32D cells stably expressing IRS-2 and the insulin receptor (IR). These results suggest that growth inhibition by TGF-beta1 involves IRS proteins.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division
  • Cell Line
  • Cell Line, Tumor
  • DNA / biosynthesis
  • DNA / metabolism
  • DNA, Complementary / metabolism
  • Dose-Response Relationship, Drug
  • Insulin / metabolism
  • Insulin Receptor Substrate Proteins
  • Integrin alpha5beta1 / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Leukemia Virus, Murine
  • Mice
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Precipitin Tests
  • Protein Binding
  • Receptor, Insulin / metabolism
  • Signal Transduction
  • Transfection
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta1

Substances

  • DNA, Complementary
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Integrin alpha5beta1
  • Intracellular Signaling Peptides and Proteins
  • Irs1 protein, mouse
  • Irs2 protein, mouse
  • Phosphoproteins
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • DNA
  • Receptor, Insulin