Modification of the sialic acid residues of choriogonadotropin affects signal transduction.
Human choriogonadotropin (hCG) is a glycoprotein hormone that activates adenylyl cyclase. The carbohydrate moieties of hCG are required for biological activity, but not for binding to the gonadotropin receptors. We modified N-acetylneuraminic acid (NeuAc) on the oligosaccharide moieties of hCG, and determined the effect on its biological activity by measuring hormone-stimulated adenylyl cyclase. Treating hCG with sodium periodate to remove two carbon atoms from NeuAc or quantitatively removing NeuAc from hCG reduced its biological activity by 36% and 50%, respectively. The galactose residues of asialo-hCG were reacted with NeuAc-hydrazone or a hydrazone of the oligosaccharide from the ganglioside GM1 (Gal(beta 1-3)GalNAc(beta 1-4) [NeuAc(alpha 2-3)]Gal(beta 1-4)Glc). The gonadotropin receptor had high affinity for both derivatives, but their biological activity was less than that of hCG. These results suggest that several structural aspects of NeuAc including carbon side chain, an intact ring structure, and the position of NeuAc relative to other carbohydrate residues are important for full biological activity of hCG.
Reddy
B V
BV
Membrane Biochemistry Section, NINDS, NIH, Bethesda, MD 20892, USA.
Bartoszewicz
Z
Z
Rebois
R V
RV
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001212:Asialoglycoproteins / Q000737:chemistry / Q000494:pharmacology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000032:analysis; D002460:Cell Line; D002772:Cholera Toxin / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000737:chemistry / Q000187:drug effects* / Q000494:pharmacology / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D005677:G(M1) Ganglioside / Q000502:physiology; D005692:Galactose Oxidase / Q000494:pharmacology; D006031:Glycosylation; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid; D010084:Oxidation-Reduction; D010504:Periodic Acid / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D012794:Sialic Acids / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D001212:Asialoglycoproteins; D002241:Carbohydrates; D006063:Chorionic Gonadotropin; D012794:Sialic Acids; C019263:asialo-human chorionic gonadotropin; D010504:Periodic Acid; D005677:G(M1) Ganglioside; D002772:Cholera Toxin; C009288:metaperiodate; D005692:Galactose Oxidase; D000262:Adenylyl Cyclases; D019158:N-Acetylneuraminic Acid