title: Biochemical roles of the oligosaccharide chains in thyrostimulin, a heterodimeric hormone of glycoprotein hormone subunits alpha 2 (GPA2) and beta 5 (GPB5).
abstract: Thyrostimulin is a heterodimeric hormone composed of GPA2 and GPB5, and shares the thyroid-stimulating hormone receptor (TSHR). Thyrostimulin has three N-linked oligosaccharide chains, two in GPA2 and one in GPB5. The roles of these N-linked oligosaccharides in secretion, heterodimer formation and signal transduction were analyzed. Recombinant GPA2s lacking either of the two oligosaccharides were obtained from conditioned medium, whereas dual site-disrupted GPA2 and the GPB5 mutant were not expressed in either the conditioned medium or cell lysate. The binding between GPA2 and GPB5 was weaker than that between TSH subunits GPA1 and TSH beta. Neither of the oligosaccharides in GPA2 had significant effects on heterodimerization. Disruption of either of the oligosaccharides in GPA2 significantly decreased receptor activation, suggesting their critical role in receptor activation.
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Okajima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagasaki
authors.forename: Chizuko
authors.initials: C
authors.lastname: Suzuki
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Suga
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Ozaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arima
authors.forename: Yoji
authors.initials: Y
authors.lastname: Hamada
authors.forename: Olivier
authors.initials: O
authors.lastname: Civelli
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D019281:Dimerization; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008954:Models, Biological; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009844:Oligosaccharides / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D009844:Oligosaccharides; D021122:Protein Subunits; D011994:Recombinant Proteins; C458339:thyrostimulin; D000242:Cyclic AMP