Pro-opiomelanocortin synthesized by corticotrophs bears asparagine-linked oligosaccharides terminating with SO4-4GalNAcβ1,4GlcNAcβ1,2Manα

T. P. Skelton, S. Kumar, P. L. Smith, M. C. Beranek, J. U. Baenziger

Research output: Contribution to journalArticle

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Abstract

We have determined that ≥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- 4GalNAcβ1,4GlcNAcβ1,2Manα (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 GalNAcβ1,4GlcNAcβ1,2Man-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 α- and β-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.

Original languageEnglish
Pages (from-to)12998-13006
Number of pages9
JournalJournal of Biological Chemistry
Volume267
Issue number18
StatePublished - Jan 1 1992

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