Met binds to Fas (left) to reduce Fas-induced apoptosis (brown).

Zarnegar/Elsevier

Growth factor receptors can promote life, and now Reza Zarnegar and colleagues (University of Pittsburgh, Pittsburgh, PA) show they can also prevent death, via physical interactions with death receptors.

Hepatocyte growth factor (HGF) binds to and activates the receptor tyrosine kinase Met, which promotes cell survival by activating antiapoptotic programs such as the PI-3 kinase signaling cascade. The opposite result is triggered when Fas ligand (FasL) binds to the death receptor Fas, triggering its homotrimerization and the formation of a docking site for death-inducing factors, such as caspase-8. Aggregation of Fas independent of FasL is believed to be sufficient to initiate apoptosis, but under growth conditions is somehow prevented.Zarnegar has now shown that Met directly associates with the majority of Fas, preventing self aggregation. Additionally, Met binding masks the FasL binding site on Fas,...

The Rockefeller University Press
2002
The Rockefeller University Press
2002
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