title: Functional divergence of glycoprotein hormone receptors.
abstract: Two lamprey glycoprotein hormone receptors (lGpH-R I and II) highly similar with gnathostome GpH-Rs were cloned from sea lamprey testes and thyroid, respectively. Vertebrate glycoprotein protein receptors have a large extracellular domain (ED) containing a leu rich domain (LRD) linked to a rhodopsin-like transmembrane domain (TMD) through a highly divergent linker region (signal specificity domain, SSD or 'hinge' region) and a third major segment, the intracellular domain. To determine the potential roles of the different domains in the activation of the receptor following ligand-receptor binding, functional assays were performed on lGpH-R I/rat luteinizing hormone (LH)-R domain swapped chimeric receptors. These results show that the functional roles of the lamprey glycoprotein-receptor I (lGpH-R I) domains are conserved compared with its Gnathostome homologs. The ability of different glycoprotein hormones to activate chimeric lamprey/rat receptors suggests that the selectivity of the GpH-Rs in respect to their ligands is not controlled exclusively by a single domain but is the result of specific interactions between domains. We hypothesize that these interactions were refined during millions of years of co-evolution of the receptors with their cognate ligands under particular intramolecular, intermolecular and physiological constraints.
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Molecular and Comparative Endocrinology, University of New Hampshire, Durham, NH 03824, USA.
authors.forename: Mihael
authors.initials: M
authors.lastname: Freamat
authors.forename: Stacia A
authors.initials: SA
authors.lastname: Sower
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000378:metabolism; D007798:Lampreys / Q000378:metabolism / Q000502:physiology*; D010907:Pituitary Hormones / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011979:Receptors, Pituitary Hormone / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
chemical_list: D010907:Pituitary Hormones; D011979:Receptors, Pituitary Hormone; D011994:Recombinant Proteins; D000242:Cyclic AMP; D000469:Alkaline Phosphatase