Degradation process of ligand-stimulated platelet-derived growth factor beta-receptor involves ubiquitin-proteasome proteolytic pathway.
The platelet-derived growth factor beta-receptor undergoes polyubiquitination as a consequence of ligand binding. We have previously reported that ligand-induced ubiquitination of the receptor plays a negative regulatory role in its mitogenic signaling possibly by promoting the efficient degradation of the ligand-activated receptor (Mori, S., Heldin, C.-H., and Claesson-Welsh, L. (1993) J. Biol. Chem. 268, 577-583). In the present study, we have examined effects of different kinds of cell-penetrating proteasome inhibitors, including substrate-related peptidyl aldehydes, Cbz-Ile-Glu(O-t-Bu)-Ala-leucinal (where Bu is butyl and Cbz is benzyloxycarbonyl) (PSI) and Cbz-Leu-Leu-norvalinal (MG115), and a Streptomyces metabolite lactacystin, on degradation of the receptor in intact cells with the aim of evaluating the role of the receptor ubiquitination in the proteasome-dependent proteolytic process. These proteasome inhibitors were found to considerably inhibit ligand-stimulated degradation of the wild-type beta-receptor; however, their inhibitory effect was not observed when the cells expressing the ubiquitination-deficient mutant beta-receptor were analyzed. These data suggest that the degradation process of the ligand-stimulated beta-receptor involves the ubiquitin-proteasome proteolytic pathway.
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002738:Chloroquine / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004151:Dipeptides / Q000494:pharmacology; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011817:Rabbits; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D013552:Swine; D014452:Ubiquitins / Q000378:metabolism*
D004151:Dipeptides; D009097:Multienzyme Complexes; D014452:Ubiquitins; C067713:lactacystin; C071482:calpeptin; D002738:Chloroquine; D017479:Receptors, Platelet-Derived Growth Factor; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine