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.
Mori
S
S
Second Department of Internal Medicine, Chiba University School of Medicine, Japan.
Kanaki
H
H
Tanaka
K
K
Morisaki
N
N
Saito
Y
Y
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D009097:Multienzyme Complexes / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D017479:Receptors, Platelet-Derived Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014452:Ubiquitins / Q000378:metabolism
D015853:Cysteine Proteinase Inhibitors; D008024:Ligands; D009097:Multienzyme Complexes; D009842:Oligopeptides; D011994:Recombinant Proteins; D014452:Ubiquitins; C090535:benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal; C067713:lactacystin; D017479:Receptors, Platelet-Derived Growth Factor; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine