The asialoglycoprotein receptor is associated with a tyrosine kinase in HepG2 cells.
The asialoglycoprotein (ASGP) receptor undergoes constitutive endocytosis in HepG2 cells, which is regulated by tyrosine kinase activity (Fallon, 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 copurifies with a tyrosine kinase activity, as defined by tyrosine phosphorylation of an exogenous substrate (reduced carboxyamidomethylated and 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 addition, receptor kinase association is not dependent on the single cytoplasmic tyrosine at position 5. Analysis of the components of anti-ASGP receptor immunoprecipitates revealed the presence of a 127-kDa protein (p127), which becomes phosphorylated on tyrosine upon addition of gamma-[32P]ATP and which is capable of binding ATP.p127 was also demonstrated in anti-transferrin receptor immunoprecipitates but not in immunoprecipitates of a resident membrane protein, human HLA. In conclusion, these data demonstrate that the ASGP receptor, a protein that participates in constitutive, rapid endocytosis, is associated with a cellular tyrosine kinase.
Fallon
R J
RJ
Department of Pediatrics, St. Louis University School of Medicine, Missouri 63104.
Danaher
M
M
Saxena
A
A
D037263:Asialoglycoprotein Receptor; D001426:Bacterial Proteins / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D037263:Asialoglycoprotein Receptor; D001426:Bacterial Proteins; D010750:Phosphoproteins; C081463:RPL44E protein, Haloarcula marismortui; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; D011505:Protein-Tyrosine Kinases