c-src Tyrosine Kinase Is Associated with the Asialoglycoprotein Receptor in Human Hepatoma Cells

Abstract

The asialoglycoprotein (ASGP) receptor is expressed on hepatocytes and liver-derived cell lines and is responsible for the endocytosis of galactose-terminal glycoproteins via the coated pit pathway. Prior data showed that tyrosine kinase activity plays an important role in this endocytic process, though the critical kinase(s) responsible for this effect are unknown. We have detected a 60-kDa protein which coprecipitates with ASGP receptor in detergent-solubilized lysates of HepG2 cells. This protein autophosphorylates and binds radioactive ATP. It comigrates with authentic pp60 c-src and is recognized by a specific anti-src monoclonal antibody. The kinase associated with the ASGP receptor retains the ability to phosphorylate exogenous substrates on tyrosine. In conclusion, the tyrosine kinase c-src associates with the ASGP receptor, a protein of the coated pit pathway of endocytosis.