The intracellular region adjacent to plasma membrane (residues 684-692) of the thyrotropin receptor is important for phosphoinositide signaling but not for agonist-induced adenylate cyclase activation.
We investigated the role of the intracellular region adjacent to transmembrane helix VII of the thyrotropin receptor (TSHR) in signal transduction using mutants as we did on the cytoplasmic loops. Two mutants with a substitution of the alpha 1- or beta 2-adrenergic receptor sequence showed a TSH- or Graves' IgG-stimulated cAMP response despite a low TSH binding Bmax. Both the mutants completely lost or markedly decreased the TSH- or Graves' IgG-stimulated inositol phosphate increase. These findings suggest that the intracellular region adjacent to the transmembrane region (residues 684-692) of the TSHR does not play a crucial role in agonist-induced adenylate cyclase activation but that it is important for phosphoinositide signaling.
Kosugi
S
S
Department of Laboratory Medicine, Kyoto University School of Medicine, Japan.
Mori
T
T
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D006111:Graves Disease / Q000097:blood / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010716:Phosphatidylinositols / Q000378:metabolism*; D017433:Protein Structure, Secondary; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000737:chemistry / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D013972:Thyrotropin / Q000494:pharmacology*; D014162:Transfection
D007074:Immunoglobulin G; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D018340:Receptors, Adrenergic, alpha-1; D018343:Receptors, Adrenergic, beta-2; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases