Mutual interaction and reciprocal down-regulation between c-met and insulin receptor substrate-1.
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.
DeAngelis
Tiziana
T
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Morrione
Andrea
A
Baserga
Renato
R
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D055504:Insulin Receptor Substrate Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases