Pro-opiomelanocortin synthesized by corticotrophs bears asparagine-linked oligosaccharides terminating with SO4-4GalNAc beta 1,4GlcNAc beta 1,2Man alpha.
We have determined that greater than or equal to 80% of the Asn-linked oligosaccharides on the glycosylated form of mouse adrenocorticotropin (15-kDa adrenocorticotropin (ACTH)) bear one or more branches terminating with the sequence SO4-4GalNAc beta 1,4GlcNAc beta 1,2Man alpha (S4GGnM). Proopiomelanocortin (POMC), the precursor of ACTH, is the first example of a glycoprotein that is not a member of the glycoprotein hormone family to bear such sulfated structures. Like lutropin and thyrotropin, 15-kDa ACTH bears dibranched oligosaccharides terminating with SO4-4-GalNAc; however, at least half of the oligosaccharides on 15-kDa ACTH terminating with SO4-4-GalNAc consist of more highly branched structures that have not previously been described. Both the GalNAc beta 1,4GlcNAc beta 1,2Man-4-sulfotransferase and the glycoprotein hormone-specific GalNAc-transferase are expressed in the corticotroph-derived AtT-20 cell line. A tripeptide recognition sequence, Pro-Val-Lys, similar to the Pro-Leu-Arg sequence required for recognition of glycoprotein hormone alpha- and beta-subunits by the glycoprotein hormone-specific GalNAc-transferase, is present 8 residues amino-terminal to the glycosylated Asn of 15-kDa ACTH. Thus, POMC has the features expected for specific addition of the S4GGnM sequence to its oligosaccharides. The recent discovery of a receptor in hepatic endothelial cells that recognizes oligosaccharides terminating with S4GGnM suggests these sulfated oligosaccharides will regulate the circulatory half-life of glycosylated POMC cleavage products.
Skelton
T P
TP
Department of Pathology, Washington University Medical School, St. Louis, Missouri 63110.
Kumar
S
S
Smith
P L
PL
Beranek
M C
MC
Baenziger
J U
JU
D000595:Amino Acid Sequence; D001216:Asparagine / Q000737:chemistry*; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005455:Fluorescent Antibody Technique; D008969:Molecular Sequence Data; D017350:N-Acetylgalactosaminyltransferases / Q000378:metabolism; D009844:Oligosaccharides / Q000096:biosynthesis* / Q000737:chemistry; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D011233:Precipitin Tests; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000737:chemistry; D015238:Sulfotransferases / Q000378:metabolism
D009844:Oligosaccharides; D011333:Pro-Opiomelanocortin; D001216:Asparagine; D017350:N-Acetylgalactosaminyltransferases; C072136:glycoprotein hormone-specific N-acetylgalactosamine transferase; C092527:N-acetylgalactosamine-4-sulfotransferase; D015238:Sulfotransferases