Expression and phosphorylation of rat c-met/hepatocyte growth factor receptor during rat liver regeneration

Hepatocyte growth factor receptor is identified as a heterodimeric tyrosine kinase encoded by the c-met gene. This study was designed to determine how the c-met/hepatocyte growth factor receptor participates in the intracellular events involved in rat liver regeneration induced by administration of carbon tetrachloride. Expression of the rat c-met mRNA increased, peaking 24 h after carbon tetrachloride administration almost in parallel with MET protein expression. Histochemical studies demonstrated that expression of the rat c-met was enhanced in cells surrounding the damaged areas, and also that the distribution of cells expressing MET was almost in accordance with that of cells expressing proliferating cells nuclear antigen. The MET protein underwent intense tyrosine phosphorylation peaking at 12 h after carbon tetrachloride administration, and prior to DNA synthesis. Phospholipase C gamma and phosphatidylinositol 3-kinase, intracellular signal transducing molecules containing Src homology 2 domain, were associated with the MET protein following tyrosine phosphorylation in vivo. These observations suggest that expression and tyrosine phosphorylation of MET protein associated with signal transducing molecules may provide a mechanism whereby hepatocyte growth factor exerts its action on hepatocyte growth during rat liver regeneration induced by carbon tetrachloride administration.