Ligand-activated platelet-derived growth factor beta-receptor is degraded through proteasome-dependent proteolytic pathway.

The platelet-derived growth factor beta-receptor undergoes polyubiquitination as a consequence of ligand binding. Ubiquitin conjugation to protein is implicated in proteasome-dependent proteolytic pathway for short-lived proteins. In the present study, we have examined effects of different kinds of cell-penetrating proteasome inhibitors, including N-benzyloxycarbonyl-L-isoleucyl-gamma-t-butyl-L-glutamyl-L-alanyl-L-l eucinal (PSI) and a Streptomyces metabolite lactacystin, on ligand-stimulated degradation of the beta-receptor. These proteasome inhibitors were found to considerably inhibit the degradation of autophosphorylated and polyubiquitinated receptors, suggesting the possible involvement of proteasomes in the degradation process of the ligand-activated beta-receptor.