A src-related kinase in the brush border membranes of gastrointestinal cells is regulated by c-met

Hepatocyte growth factor (HGF) elicits pleiotropic cellular responses by binding to c-met, a PTK transmembrane receptor. The recent identification of HGF in fluids which enter the gut lumen suggests a mechanism by which c-met molecules are accessible to ligand that is present near the apical surfaces of polarized enterocytes. A subset of c-met molecules was detected, by confocal and immunoelectron microscopic analysis, which colocalizes with a recently identified src-related gastrointestinal tyrosine kinase (gtk) in the brush border membranes of enterocytes. Furthermore, treatment of c-met/gtk-transfected cells with a chemical cross-linking agent revealed that c-met forms a physical complex with gtk, in vivo. Not surprisingly, activation of the receptor molecules with HGF rapidly stimulated gtk enzymatic activity. Similarly, the stimulation of gtk activity occurred when nontransfected primary hepatocytes were exposed to ligand. These findings suggest a model in which HGF binding to luminally accessible c-met stimulates gtk activity. This brush border-associated c-met-linked pathway may be associated with a defined set of epithelial cell responses.