Synergistic action of R-Ras and IGF-1 on Bcl-xL expression and caspase-3 inhibition in BaF3 cells: R-Ras and IGF-1 control distinct anti-apoptotic kinase pathways

FEBS Lett. 1998 Oct 16;437(1-2):112-6. doi: 10.1016/s0014-5793(98)01213-7.

Abstract

R-Ras and insulin-like growth factor-1 (IGF-1) synergistically inhibit apoptosis of BaF3 cells upon interleukin-3 deprivation. To characterize the mechanism of this synergistic inhibition, we examined the effect of R-Ras and IGF-1 on several apoptosis-related proteins. Extracellular signal-regulated kinase (ERK) was activated by IGF-1, but not by R-Ras. In contrast, Akt was activated strongly by R-Ras, but weakly by IGF-1. It was also found that R-Ras and IGF-1 cooperatively induced Bcl-xL expression and inhibited caspase-3 activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Caspase 3
  • Caspases / metabolism*
  • Cells, Cultured
  • Drug Synergism
  • GTP Phosphohydrolases / pharmacology*
  • Gene Expression Regulation
  • Insulin-Like Growth Factor I / pharmacology*
  • Interleukin-3 / pharmacology
  • Mitogen-Activated Protein Kinases / metabolism*
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • bcl-X Protein
  • ras Proteins / pharmacology*

Substances

  • Interleukin-3
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein
  • Insulin-Like Growth Factor I
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • GTP Phosphohydrolases
  • ras Proteins