The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAcβ1,4GlcNAcβ1,2Manα

P. L. Smith, T. P. Skelton, D. Fiete, S. M. Dharmesh, M. C. Beranek, L. MacPhail, G. J. Broze, J. U. Baenziger

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Abstract

Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains sulfated Asn-linked oligosaccharides. We have determined that >70% of the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with the sequence SO4-4GalNAcβ1,4GlcNAcβ1,2Manα. Oligosaccharides terminating with this sequence have previously been described on lutropin, thyrotropin, and pro-opiomelanocortin: glycoproteins synthesized in the anterior pituitary. A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa-Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the specific addition of GalNAc to the oligosaccharide acceptor on these glycoproteins, whereas a GalNAcβ1,4GlcNAcβ1,2Manα-4-sulfotransferase accounts for the addition of sulfate. The sulfated oligosaccharides present on these hormones are responsible for their rapid clearance from plasma by a receptor in hepatic reticuloendothelial cells. GalNAc- and sulfotransferase activities with the same properties as those expressed in the pituitary are detected at high levels in 293 cells and at lower levels in endothelial cells. Chinese hamster ovary (CHO) cells do not contain detectable levels of either transferase and rTFPI expressed in CHO cells does not contain sulfated Asn-linked oligosaccharides. TFPI contains the sequence Pro-Phe-Lys, 9 residues N-terminal to the glycosylation site at position 228; this tripeptide may act as the recognition sequence for the GalNAc-transferase. rTFPI produced by 293 cells, but not that produced by CHO cells, is bound by the receptor on hepatic reticuloendothelial cells suggesting the sulfated structures play a role in the biologic behavior of TFPI.

Original languageEnglish
Pages (from-to)19140-19146
Number of pages7
JournalJournal of Biological Chemistry
Volume267
Issue number27
StatePublished - Jan 1 1992

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    Smith, P. L., Skelton, T. P., Fiete, D., Dharmesh, S. M., Beranek, M. C., MacPhail, L., Broze, G. J., & Baenziger, J. U. (1992). The asparagine-linked oligosaccharides on tissue factor pathway inhibitor terminate with SO4-4GalNAcβ1,4GlcNAcβ1,2Manα. Journal of Biological Chemistry, 267(27), 19140-19146.