THE ASIALOGLYCOPROTEIN RECEPTOR IS ASSOCIATED WITH A TYROSINE KINASE IN HEPG2 CELLS

The asialoglycoprotein (ASGP) receptor undergoes constitutive endocyto sis in HepG2 cells, which is regulated by tyrosine kinase activity (Fa llen, R. J., Danaher, M., Saylors, R. L., and Saxena, A (1994) J. Biol . Chem. 269, 11011-11017). In this study we show that the receptor cop urifies with a tyrosine kinase activity, as defined by tyrosine phosph orylation of an exogenous substrate (reduced carboxyamidomethylated an d maleylated lysozyme). Analysis of cells transfected with one subunit of the ASGP receptor showed that signals in the cytoplasmic domain of the H1 subunit are sufficient for receptor kinase association. In add ition, receptor kinase association is not dependent on the single cyto plasmic tyrosine at position 5. Analysis of the components of anti-ASG P receptor immunoprecipitates revealed the presence of a 127-kDa prote in (p127), which becomes phosphorylated on tyrosine upon addition of g amma-[P-32]ATP and which is capable of binding ATP. p127 was also demo nstrated in anti-transferrin receptor immunoprecipitates but not in im munoprecipitates of a resident membrane protein, human HLA. In conclus ion, these data demonstrate that the ASGP receptor, a protein that par ticipates in constitutive, rapid endocytosis, is associated with a cel lular tyrosine kinase.