Differential glycosylation of N-POMC1-77 regulates the production of gamma 3-MSH by purified pro-opiomelanocortin converting enzyme. A possible mechanism for tissue-specific processing.
The amino terminus of bovine pro-opiomelanocortin (N-POMC1-77) is partially processed in the intermediate lobe of the pituitary to N-POMC1-49 and lys-gamma 3-melanotropin. Two pools of N-POMC1-77 were isolated which were differentially glycosylated at threonine45, while N-POMC1-49 isolated from bovine intermediate lobe extracts existed in a non-glycosylated form. This suggested that differential O-linked glycosylation of N-POMC1-77 may regulate cleavage at the Arg49-Lys50 processing site. We tested this hypothesis by incubating N-POMC1-77 glycoforms with purified proopiomelanocortin converting enzyme. Only non-O-glycosylated N-POMC1-77 and O-glycosylated N-POMC1-77 with truncated oligosaccharide sidechains were sensitive to cleavage and generated predominantly lys-gamma 3-melanotropin, identified by high-performance liquid chromatography. These data provide the first functional evidence to support a role for differential O-linked glycosylation in the regulation of the processing of the N-terminus of bovine POMC.
Birch
N P
NP
Section on Cellular Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Estivariz
F E
FE
Bennett
H P
HP
Loh
Y P
YP
D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D010450:Endopeptidases / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D066298:In Vitro Techniques; D009074:Melanocyte-Stimulating Hormones / Q000096:biosynthesis*; D010904:Pituitary Gland, Posterior / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000737:chemistry / Q000378:metabolism*; D043484:Proprotein Convertases; D011499:Protein Processing, Post-Translational; D013329:Structure-Activity Relationship
D006023:Glycoproteins; D011333:Pro-Opiomelanocortin; D009074:Melanocyte-Stimulating Hormones; D010450:Endopeptidases; D043484:Proprotein Convertases