Sm. Manzella et al., EVOLUTIONARY CONSERVATION OF THE SULFATED OLIGOSACCHARIDES ON VERTEBRATE GLYCOPROTEIN HORMONES THAT CONTROL CIRCULATORY HALF-LIFE, The Journal of biological chemistry, 270(37), 1995, pp. 21665-21671
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.