title: Two defective heterozygous luteinizing hormone receptors can rescue hormone action.
abstract: Luteinizing hormone receptor is a G protein-coupled receptor and consists of two halves: the N-terminal extracellular half (exodomain) and C-terminal membrane-associated half (endodomain). Hormone binds to the exodomain, and the resulting hormone-exodomain complex modulates the endodomain to generate signals. There are mutations that impair either hormone binding or signal generation. We report that the coexpression of a binding defective mutant and a signal-defective mutant rescues signal generation to produce cAMP. This rescue requires both types of mutant receptors and is dependent on the human chorionic gonadotropin dose, the surface concentration of mutant receptors, and the amino acid position of mutations. Furthermore, random collisions among mutant receptors are not involved in the rescue. Our observations provide new insights into the mechanisms of the functional and structural relationship of the exo- and endodomain, signal transduction, and receptor genetics, in particular for defective heterozygotes.
authors.affiliation: Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055, USA.
authors.forename: ChangWoo
authors.initials: C
authors.lastname: Lee
authors.forename: Inhae
authors.initials: I
authors.lastname: Ji
authors.forename: KiSung
authors.initials: K
authors.lastname: Ryu
authors.forename: YongSang
authors.initials: Y
authors.lastname: Song
authors.forename: P Michael
authors.initials: PM
authors.lastname: Conn
authors.forename: Tae H
authors.initials: TH
authors.lastname: Ji
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007700:Kinetics; D009154:Mutation; D051381:Rats; D011974:Receptors, LH / Q000235:genetics* / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
chemical_list: D006063:Chorionic Gonadotropin; D018076:DNA, Complementary; D011974:Receptors, LH; D011994:Recombinant Proteins; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D019204:GTP-Binding Proteins