Mutual interaction and reciprocal down-regulation between c-met and insulin receptor substrate-1

J Cell Physiol. 2010 Sep;224(3):658-63. doi: 10.1002/jcp.22164.

Abstract

The insulin receptor substrate-1 (IRS-1) and c-met, the receptor for the hepatocyte growth factor (HGF) co-immuno-precipitate from lysates treated with the respective antibodies. The interaction between IRS-1 and c-met requires a tyrosyl phosphorylated IRS-1 and results in reciprocal down-regulation. IRS-1 inhibits cell motility, while the activated c-met promotes it. These and other results suggest an explanation for reports in the literature indicating that c-met levels are high and IRS-1 levels are low in human cancer metastases.

MeSH terms

  • Animals
  • Cell Line
  • Cell Movement / physiology
  • Down-Regulation*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Insulin Receptor Substrate Proteins / genetics
  • Insulin Receptor Substrate Proteins / metabolism*
  • Mice
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / metabolism*
  • Signal Transduction / physiology

Substances

  • Insulin Receptor Substrate Proteins
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases