THE RELATIONSHIP OF LIGAND RECEPTOR MOBILITY TO INTERNALIZATION OF POLYPEPTIDE HORMONES AND GROWTH-FACTORS

Polypeptide hormones and growth factors bind to cell surface receptors and are internalized by receptor-mediated endocytosis. Both [I-125]insulin and [I-125]epidermal growth factor (EGF) are internalized to a much greater extent than [I-125]glucagon in freshly isolated rat hepatocytes. All three ligands bind initially and preferentially to the microvillous surface of the hepatocyte, but only [I-125]insulin and [I-125]EGF undergo significant redistribution to the nonvillous surface of the cell. Thus, the degree of lateral mobility of the ligand receptor complex is strongly correlated with the extent of internalization of the ligand. Since the beta-subunit of the insulin and the EGF receptors span the plasma membrane only once and both receptors are autophosphorylated, it is possible that these are important determinants of the receptor mobility.