Intracellular association of a mutant insulin-like growth factor receptor with endogenous receptors

Clin Cancer Res. 2001 Jul;7(7):2134-44.

Abstract

The type 1 insulin-like growth factor receptor (IGF-IR) is emerging as a powerful survival factor against a variety of apoptotic agents in many cell types. A mutant IGF-IR designated 486/STOP is known to induce apoptosis and inhibit the growth of human tumor cells in mice. We have investigated the mechanism of action of 486/STOP. To study it, we have developed a new retroviral vector in which we have combined a self-inactivating 5'-long terminal repeat with an inducible heat-shock promoter (heat shock protein 70) from Drosophila. Using this technique, we find that the polypeptide encoded by 486/STOP is partially retained within the cell and partially secreted. However, the secreted polypeptide is subsequently taken up by the cells. In both cases, a specific intracellular interaction of 486/STOP with the endogenous IGF-IRs can be demonstrated by coimmunoprecipitation.

Publication types

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

MeSH terms

  • Agar / pharmacology
  • Animals
  • Apoptosis / genetics
  • Cell Count
  • Cell Division / drug effects
  • Cell Division / genetics
  • Cell Line
  • Culture Media, Conditioned / chemistry
  • Gene Expression
  • Genotype
  • Microscopy, Confocal
  • Mutation
  • Plasmids / genetics
  • Protein Binding
  • Receptor, IGF Type 1 / genetics*
  • Receptor, IGF Type 1 / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism

Substances

  • Culture Media, Conditioned
  • Recombinant Fusion Proteins
  • Agar
  • Receptor, IGF Type 1