title: Multiple interactions between pituitary hormones and the mannose receptor.
abstract: The macrophage mannose receptor, which has a well-documented role in the innate immune system, has an additional function in the clearance of pituitary hormones. Clearance is mediated by the recognition of sulphated terminal N-acetylgalactosamine residues (SO(4)-4GalNAc) on the hormones. Previous studies with an SO(4)-4GalNAc-containing neoglycoprotein suggest that the SO(4)-4GalNAc-binding site is localized to the N-terminal cysteine-rich domain of the receptor, distinct from the mannose/N-acetylglucosamine/fucose-specific C-type carbohydrate-recognition domains (CRDs). The present study characterizes the binding of natural pituitary hormone ligands to a soluble portion of the mannose receptor consisting of the whole extracellular domain and to a truncated form containing the eight CRDs but lacking the N-terminal cysteine-rich domain and the fibronectin type II repeat. Both forms of the receptor show high-affinity saturable binding of lutropin and thyrotropin. Binding to the full-length receptor is dependent on pH and ionic strength and is inhibited effectively by SO(4)-4GalNAc but only partly by mannose. In contrast, binding to the truncated form of the receptor, which is also dependent on pH and ionic strength, is inhibited by mannose but not by SO(4)-4GalNAc. The results are consistent with the presence of an SO(4)-4GalNAc-specific binding site in the cysteine-rich domain of the mannose receptor but indicate that interactions between other sugars on the hormones and the CRDs are also important in hormone binding.
authors.affiliation: Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.
authors.forename: D Z
authors.initials: DZ
authors.lastname: Simpson
authors.forename: P G
authors.initials: PG
authors.lastname: Hitchen
authors.forename: E L
authors.initials: EL
authors.lastname: Elmhirst
authors.forename: M E
authors.initials: ME
authors.lastname: Taylor
mesh_terms: D000116:Acetylgalactosamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D037181:Lectins, C-Type; D008024:Ligands; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008358:Mannose / Q000378:metabolism / Q000494:pharmacology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009005:Monosaccharides / Q000378:metabolism / Q000494:pharmacology; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010907:Pituitary Hormones / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D012995:Solubility; D013972:Thyrotropin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D037181:Lectins, C-Type; D008024:Ligands; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009005:Monosaccharides; D010446:Peptide Fragments; D010907:Pituitary Hormones; D011956:Receptors, Cell Surface; C046735:N-acetylgalactosamine 4-sulfate; D007986:Luteinizing Hormone; D013972:Thyrotropin; D003545:Cysteine; D000116:Acetylgalactosamine; D008358:Mannose; D002118:Calcium