The HGF receptor family: unconventional signal transducers for invasive cell growth

Abstract

The HGF receptor family includes tyrosine kinases encoded by three oncogenes: MET, SEA and RON. The members of this gene family share a unique functional feature: they mediate cell dissociation and motility ('scattering') in physiological conditions, and invasiveness in their activated versions. The Met, Ron and Sea receptors display a distinctive signal transduction behaviour. Unlike conventional growth factor receptors, their cytoplasmic tails contain a multifunctional docking site. Upon autophosphorylation, this sequence simultaneously binds and activates multiple SH2-containing transducers, including Ras and PI 3-kinase. A deregulated activation of this 'supersite' triggers a dramatic pleiotropic signal which is responsible for invasive cell growth.