title: The first cytoplasmic loop of the thyrotropin receptor is important for phosphoinositide signaling but not for agonist-induced adenylate cyclase activation.
abstract: We investigated the role of the 1st cytoplasmic loop of the thyrotropin receptor (TSHR) on signal transduction using mutants as we did the 2nd and 3rd cytoplasmic loops [Kosugi S. et al. (1994) Mol. Endocrinol., in press; and 7, 1009-1020]. Five substitution mutants involving the first cytoplasmic loop showed a TSH- or Graves' IgG-stimulated cAMP response despite the low TSH binding Bmax. All the mutants completely lost or markedly decreased the TSH- or Graves' IgG-stimulated inositol phosphate increase. These findings suggest that the 1st cytoplasmic loop of the TSHR does not play a crucial role in agonist-induced adenylate cyclase activation but that it is important for phosphoinositide signaling.
authors.affiliation: Department of Laboratory Medicine, Kyoto University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kosugi
authors.forename: T
authors.initials: T
authors.lastname: Mori
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D007074:Immunoglobulin G / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010716:Phosphatidylinositols / Q000378:metabolism*; D011989:Receptors, Thyrotropin / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013972:Thyrotropin / Q000378:metabolism
chemical_list: D007074:Immunoglobulin G; D010716:Phosphatidylinositols; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases