Ligand-induced polyubiquitination of the platelet-derived growth factor beta-receptor.
We have analyzed the nature of ligand-induced shift to higher molecular weight forms of the beta-receptor for platelet-derived growth factor expressed in porcine aortic endothelial cells. The modification of the beta-receptor was found to be due to polyubiquitination, as judged by immunoblotting using an anti-ubiquitin antiserum. A mutant beta-receptor made kinase negative by a point mutation (K634A mutant) did not undergo ubiquitination in response to ligand stimulation. A mutant in which carboxyl-terminal 98 amino acids were deleted (CT98 mutant) and which retained kinase activity was likewise not ubiquitinated. These data suggest that the kinase activity, as well as the carboxyl-terminal 98 amino acids, is required for ubiquitination of the beta-receptor. Ligand-induced degradation of the receptor-bound ligand, as well as of the receptor itself, was partially impaired in the CT98-receptor-expressing cells, suggesting that the ubiquitination is of importance for efficient degradation of the ligand-receptor complex.
Mori
S
S
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Heldin
C H
CH
Claesson-Welsh
L
L
D000818:Animals; D001011:Aorta; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007700:Kinetics; D008024:Ligands; D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D013552:Swine; D014162:Transfection; D014452:Ubiquitins / Q000378:metabolism*
D008024:Ligands; D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D014452:Ubiquitins; D011494:Protein Kinases; D017479:Receptors, Platelet-Derived Growth Factor