LIGAND-ACTIVATED PLATELET-DERIVED GROWTH-FACTOR BETA-RECEPTOR IS DEGRADED THROUGH PROTEASOME-DEPENDENT PROTEOLYTIC PATHWAY

The platelet-derived growth factor beta-receptor undergoes polyubiquit ination as a consequence of ligand binding. Ubiquitin conjugation to p rotein is implicated in proteasome-dependent proteolytic pathway for s hort-lived proteins. In the present study, we have examined effects of different kinds of cell-penetrating proteasome inhibitors, including isoleucyl-Y-t-butyl-L-glutamyl-L-alanyl-L-leucinal (PSI) and a Strepto myces metabolite lactacystin, on ligand-stimulated degradation of the beta-receptor. These proteasome inhibitors were found to considerably inhibit the degradation of autophosphorylated and polyubiquitinated re ceptors, suggesting the possible involvement of proteasomes in the deg radation process of the ligand-activated beta-receptor. (C) 1995 Acade mic Press, Inc.