A TYROSINE RESIDUE IN THE JUXTAMEMBRANE SEGMENT OF THE PLATELET-DERIVED GROWTH-FACTOR BETA-RECEPTOR IS CRITICAL FOR LIGAND-MEDIATED ENDOCYTOSIS

The importance of tyrosine residues in ligand-mediated endocytosis of the platelet-derived growth factor beta-receptor was analyzed using a series of tyrosine residue-mutated beta-receptors, which together cove r all of the tyrosine residues in the juxtamembrane segment, the kinas e insert, and the carboxyl-terminal tail; also certain of the tyrosine residues within the first and second parts of the kinase domain were examined. Of all of these tyrosine residues, only Tyr-579 seemed to be important for internalization, since mutation of this residue resulte d in substantial reduction in the rate of ligand-induced receptor inte rnalization (approximate to 60% of the wild-type level). Replacement o f Tyr-579 by either an aromatic (Phe) or a nonaromatic (Asp) residue r educed the efficiency of the mutant receptors in internalization to th e same extent, suggesting that the role of Tyr-579 in the beta-recepto r is different from that of the previously described tyrosine-based in ternalization motifs, which were first determined for the low density lipoprotein receptor. Tyr-579 has been found to be an autophosphorylat ion site in the beta-receptor. Moreover, the internalization rate of a kinase negative receptor mutant was not altered by the additional mut ation of Tyr-579. Thus, it is likely that phosphorylation of Tyr-579 i s important for ligand-induced internalization of the beta-receptor.