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

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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.