EVOLUTIONARY CONSERVATION OF THE SULFATED OLIGOSACCHARIDES ON VERTEBRATE GLYCOPROTEIN HORMONES THAT CONTROL CIRCULATORY HALF-LIFE

The circulatory half-life of the mammalian glycoprotein hormone lutrop in is controlled by its unique Asn-linked oligosaccharides, which term inate with the sequence SO4-4-GalNAc beta 1,4GlcNAc. A cluster of basi c amino acids essential for recognition of the alpha subunit by the gl ycoprotein hormone:N-acetylgalactosaminyltransferase is located within two turns of an alpha helix (Mengeling, B. J., Manzella, S. M., and B aenziger, J. U. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 502-506). T he amino acids within this region are virtually invariant in the alpha subunits of all vertebrates, indicating that the recognition determin ant utilized by the N-acetylgalactosaminyltransferase has been conserv ed in species ranging from teleost fish to mammals. We demonstrate tha t the glycoprotein hormone:N-acetylgalactosaminyltransferase and the N -acetylgalactosamine-4-sulfotransferase responsible for the synthesis of these unique sulfated oligosaccharides are expressed in the pituita ries of vertebrates ranging from teleost fish to mammals. Furthermore, we show that Asn-linked oligosaccharides terminating with SO4-4-GalNA c beta 1,4GlcNAc are present on the alpha and beta subunits of the sal mon glycoprotein hormone GTH II. Asn-linked oligosaccharides terminati ng with SO4-4-GalNAc beta 1,4GlcNAc are unique structural features of the glycoprotein hormones that have been conserved during vertebrate e volution, suggesting they are critical for the expression of hormone b iologic activity.