HGF receptor associates with the anti-apoptotic protein BAG-1 and prevents cell death

EMBO J. 1996 Nov 15;15(22):6205-12.

Abstract

The mechanisms by which apoptosis is prevented by survival factors are largely unknown. Using an interaction cloning approach, we identified a protein that binds to the intracellular domain of the hepatocyte growth factor (HGF) receptor. This protein was identified as BAG-1, a recently characterized Bcl-2 functional partner, which prolongs cell survival through unknown mechanisms. Overexpression of BAG-1 in liver progenitor cells enhances protection from apoptosis by HGF. Association of the receptor with BAG-1 occurs in intact cells, is mediated by the C-terminal region of BAG-1 and is independent from tyrosine phosphorylation of the receptor. Formation of the complex is increased rapidly following induction of apoptosis. BAG-1 also enhances platelet-derived growth factor (PDGF)-mediated protection from apoptosis and associates with the PDGF receptor. Microinjection or transient expression of BAG-1 deletion mutants shows that both the N- and the C-terminal domains are required for protection from apoptosis. The finding of a link between growth factor receptors and the anti-apoptotic machinery fills a gap in the understanding of the molecular events regulating programmed cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins
  • Blotting, Western
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Cloning, Molecular
  • DNA-Binding Proteins
  • Etoposide / pharmacology
  • Gene Expression Regulation / genetics
  • Liver / growth & development
  • Liver / metabolism
  • Mice
  • Mutation / genetics
  • Phosphorylation
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor Protein-Tyrosine Kinases / pharmacology
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Staurosporine / pharmacology
  • Transcription Factors
  • Transfection / genetics
  • Tyrosine / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • BCL2-associated athanogene 1 protein
  • Carrier Proteins
  • DNA-Binding Proteins
  • TP53BP2 protein, human
  • Transcription Factors
  • Tyrosine
  • Etoposide
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Platelet-Derived Growth Factor
  • Staurosporine