Glycoprotein hormone GalNAc-4-sulphotransferase.
The glycoprotein hormones lutropin (LH) and thyrotropin and a limited number of additional glycoproteins bear carbohydrate structures terminating with the unique sequence SO(4)-4-GalNAcbeta1,4GlcNAcbeta that has been conserved in the glycoprotein hormones of all vertebrate species. Synthesis of these structures is mediated by a protein-specific beta1,4GalNAc-transferase and a GalNAc-4-sulphotransferase (GalNAc-4-ST1). GalNAc-4-ST1 is a member of a family of sulphotransferases that includes HNK-1 sulphotransferase, chondroitin-4-sulphotransferases-1-3 and dermatan-4-sulphotransferase-1. With the exception of HNK-1-ST, these sulphotransferases add sulphate to the C-4 hydroxy group of either terminal or non-terminal beta1,4-linked GalNAc. GalNAc-4-ST1 is most highly expressed in pituitary, cerebellum and other regions of the brain. The terminal GalNAcSO(4) on LH is recognized by the cysteine-rich domain of the mannose/GalNAc-4-SO(4) receptor located in hepatic endothelial cells. Each cysteine-rich domain binds a single terminal GalNAc-4-SO(4), and the receptor must form non-covalently associated homodimers in order to simultaneously engage two GalNAc-4-SO(4) moieties on separate oligosaccharides with sufficient affinity to form stable complexes. The receptor mediates the clearance of LH from the blood. This clearance, in conjunction with the stimulated release of hormone from dense core granules in pituitary gonadotroph cells, is required to produce the episodic rise and fall in LH levels needed for optimal oestrogen production during the implantation of embryos in the uterus.
Baenziger
J U
JU
Washington University Medical School, Department of Pathology, St. Louis, MO 63110, U.S.A. Baenziger@pathology.wustl.edu
D000116:Acetylgalactosamine / Q000031:analogs & derivatives*; D000818:Animals; D006023:Glycoproteins / Q000096:biosynthesis; D006728:Hormones / Q000096:biosynthesis*; D006801:Humans; D009844:Oligosaccharides / Q000096:biosynthesis; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014018:Tissue Distribution
D006023:Glycoproteins; D006728:Hormones; D009844:Oligosaccharides; C046735:N-acetylgalactosamine 4-sulfate; C498300:CHST9 protein, human; C092527:N-acetylgalactosamine-4-sulfotransferase; D015238:Sulfotransferases; D000116:Acetylgalactosamine