Carboxyl terminus of delta opioid receptor is required for agonist-dependent receptor phosphorylation.
The wild-type delta opioid receptor (DOR) and a carboxyl terminus-truncated mutant DOR lacking the last 31 amino acids (DOR-T) were expressed in neuroblastoma x glioma hybrid NG108-15 cells to investigate the role of the carboxyl terminus of DOR in agonist-dependent receptor phosphorylation. Stimulation of the cells with delta specific agonists significantly induced DOR phosphorylation whereas no phosphorylation of DOR-T was detected under the same conditions. Neither overexpression of G protein-coupled receptor kinases (GRK2 or GRK5) nor activation of protein kinase C promoted agonist-induced phosphorylation of DOR-T, in contrast to their strong stimulatory effect on the agonist-dependent phosphorylation of DOR. Furthermore, DOR-T failed to be internalized after agonist stimulation, probably due to its inability to be phosphorylated. Our results indicate that the carboxyl terminus of DOR is required for agonist-dependent receptor phosphorylation and the phosphorylation site(s) of DOR is likely located at its carboxyl terminus.
Zhao
J
J
National Laboratory of Medical Neurobiology, Shanghai Medical University, China.
Pei
G
G
Huang
Y L
YL
Zhong
F M
FM
Ma
L
L
D000818:Animals; D004174:Diprenorphine / Q000494:pharmacology; D000939:Epitopes / Q000378:metabolism; D005910:Glioma; D051379:Mice; D009447:Neuroblastoma; D018847:Opioid Peptides / Q000819:agonists*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000939:Epitopes; D018847:Opioid Peptides; D017465:Receptors, Opioid, delta; D004174:Diprenorphine; D011493:Protein Kinase C