Reviews
TSHRHebrant A, van Staveren WC, Maenhaut C, Dumont JE, Leclere J. Genetic hyperthyroidism: hyperthyroidism due to activating TSHR mutations. Eur J Endocrinol. 2011 Jan;164(1):1-9 Pubmed | Luca P, Davide C, Daniela C, Giovanna W, Giulia G, Domenico L, Tiziana DF, Marco B Genetics and phenomics of hypothyroidism due to TSH resistance. Mol Cell Endocrinol. 2010 Jun 30;322(1-2):72-82 Pubmed | Paus R. Exploring the "thyroid-skin connection": concepts, questions, and clinical relevance. J Invest Dermatol. 2010 Jan;130(1):7-10 Pubmed | Biebermann H, Winkler F, Kleinau G. Genetic defects, thyroid growth and malfunctions of the TSHR in pediatric patients. Front Biosci. 2010 Jun 1;15:913-33 Pubmed | Kleinau G, Krause G. Thyrotropin and homologous glycoprotein hormone receptors: structural and functional aspects of extracellular signaling mechanisms. Endocr Rev. 2009 Apr;30(2):133-51. Pubmed | Latif R, Morshed SA, Zaidi M, Davies TF. The thyroid-stimulating hormone receptor: impact of thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibodies on multimerization, cleavage, and signaling. Endocrinol Metab Clin North Am. 2009 Jun;38(2):319-41, viii. Pubmed | Michalek K, Morshed SA, Latif R, Davies TF TSH receptor autoantibodies Autoimmun Rev. 2009 Dec;9(2):113-6. Epub 2009 Mar 27 Pubmed | Kim CS, Zhu X Lessons from mouse models of thyroid cancer. Thyroid. 2009 Dec;19(12):1317-31. Pubmed | Haugen BR. Drugs that suppress TSH or cause central hypothyroidism. Best Pract Res Clin Endocrinol Metab. 2009 Dec;23(6):793-800 Pubmed | Caltabiano G, Campillo M, De Leener A, Smits G, Vassart G, Costagliola S, Pardo L. The specificity of binding of glycoprotein hormones to their receptors. Cell Mol Life Sci. 2008 Aug;65(16):2484-92 Pubmed | García-Jiménez C, Santisteban P. TSH signalling and cancer. Arq Bras Endocrinol Metabol. 2007 Jul;51(5):654-71 Pubmed | Rapoport B, McLachlan SM The thyrotropin receptor in Graves' disease Thyroid. 2007 Oct;17(10):911-22 Pubmed | Holger Jaeschke, Maren Claus, Gunnar Kleinau, Gerd Krause, Ralf Paschke TSH-RECEPTOR STRUCTURE AND MECHANISM OF ACTIVATION HOT THYROIDOLOGY (www.hotthyroidology.com), May, No 1, 2005 Link | Terry F. Davies, Takao Ando, Reigh-Yi Lin, Yaron Tomer, and Rauf Latif Thyrotropin receptor–associated diseases: from adenomata to Graves disease J Clin Invest. 2005 August 1; 115(8): 1972–1983 Pubmed | Matsushima N, Tachi N, Kuroki Y, Enkhbayar P, Osaki M, Kamiya M, Kretsinger RH Structural analysis of leucine-rich-repeat variants in proteins associated with human diseases. Cell Mol Life Sci. 2005 Dec;62(23):2771-91 Pubmed | Vassart G, Pardo L, Costagliola S A molecular dissection of the glycoprotein hormone receptors Trends Biochem Sci. 2004 Mar;29(3):119-26 Pubmed | Gruters A, Krude H, Biebermann H Molecular genetic defects in congenital hypothyroidism Eur J Endocrinol. 2004 Nov;151 Suppl 3:U39-44 Pubmed | Rodien P, Ho SC, Vlaeminck V, Vassart G, Costagliola S Activating mutations of TSH receptor Ann Endocrinol (Paris). 2003 Feb;64(1):12-6 Pubmed | Szkudlinski MW, Fremont V, Ronin C, Weintraub BD Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships Physiol Rev. 2002 Apr;82(2):473-502 Pubmed | Corvilain B, Van Sande J, Dumont JE, Vassart G Somatic and germline mutations of the TSH receptor and thyroid diseases Clin Endocrinol (Oxf). 2001 Aug;55(2):143-58 Pubmed | Wonerow P, Neumann S, Gudermann T, Paschke R Thyrotropin receptor mutations as a tool to understand thyrotropin receptor action J Mol Med. 2001 Dec;79(12):707-21 Pubmed | Szkudlinski MW, Grossmann M, Leitolf H, Weintraub BD Human Thyroid-Stimulating Hormone: Structure-Function Analysis Methods. 2000 May;21(1):67-81 Pubmed | Farid NR, Kascur V, Balazs C The human thyrotropin receptor is highly mutable: a review of gain-of-function mutations Eur J Endocrinol. 2000 Jul;143(1):25-30 Pubmed | Rapoport B, Chazenbalk GD, Jaume JC, McLachlan SM The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies Endocr Rev. 1998 Dec;19(6):673-716 Pubmed | Laugwitz KL, Allgeier A, Offermanns S, Spicher K, Van Sande J, Dumont JE, Schultz G The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):116-20 Pubmed | Kosugi S, Sugawa H, Mori T TSH receptor and LH receptor, 1996 Endocr J. 1996 Dec;43(6):595-604 Pubmed | |
FSHRKleinau G, Krause G. Thyrotropin and homologous glycoprotein hormone receptors: structural and functional aspects of extracellular signaling mechanisms. Endocr Rev. 2009 Apr;30(2):133-51. Pubmed | Caltabiano G, Campillo M, De Leener A, Smits G, Vassart G, Costagliola S, Pardo L. The specificity of binding of glycoprotein hormones to their receptors. Cell Mol Life Sci. 2008 Aug;65(16):2484-92 Pubmed | Jeoung M, Lee C, Ji I, Ji TH Trans-activation, cis-activation and signal selection of gonadotropin receptors. Mol Cell Endocrinol. 2007 Jan 2;260-262:137-43 Pubmed | Gromoll J, Simoni M Genetic complexity of FSH receptor function Trends Endocrinol Metab. 2005 Oct;16(8):368-73 Pubmed | Themmen, A. P N. Focus on Gonadotrophin Signalling An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms Reproduction (2005) 130 263-274 Link | Costagliola S, Urizar E, Mendive F, Vassart G Specificity and promiscuity of gonadotropin receptors Reproduction. 2005 Sep;130(3):275-81 Pubmed | Dias JA. Endocrinology: fertility hormone in repose. Nature. 2005 Jan 20;433(7023):203-4 Pubmed | Vassart G, Pardo L, Costagliola S A molecular dissection of the glycoprotein hormone receptors Trends Biochem Sci. 2004 Mar;29(3):119-26 Pubmed | Dias JA, Cohen BD, Lindau-Shepard B, Nechamen CA, Peterson AJ, Schmidt A Molecular, structural, and cellular biology of follitropin and follitropin receptor Vitam Horm. 2002;64:249-322 Pubmed | Yi CS, Song YS, Ryu KS, Sohn J, Ji I, Ji TH Common and differential mechanisms of gonadotropin receptors Cell Mol Life Sci. 2002 Jun;59(6):932-40 Pubmed | Dias JA, Van Roey P Structural Biology of Human Follitropin and Its Receptor Arch Med Res. 2001 Nov-Dec;32(6):510-9 Pubmed | Themmen APN, Huhtaniemi IT Mutations of Gonadotropin and Gonadotropin Receptors: Elucidating the Physiology and Pathophysiology of Pituitary-Gonadal Function Endocr Rev. 2000 Oct;21(5):551-83 Pubmed | Levallet J, Pakarinen P, Huhtaniemi IT Follicle-Stimulating Hormone Ligand and Receptor Mutations, and Gonadal Dysfunction Arch Med Res. 1999 Nov-Dec;30(6):486-94 Pubmed | Simoni M, Gromoll J, Nieschlag E The Follicle-Stimulating Hormone Receptor: Biochemistry, Molecular Biology, Physiology, and Pathophysiology Endocr Rev. 1997 Dec;18(6):739-73 Pubmed | Gromoll J, Simoni M, Nordhoff V, Behre HM, De Geyter C, Nieschlag E Functional and clinical consequences of mutations in the FSH receptor Mol Cell Endocrinol. 1996 Dec 20;125(1-2):177-82 Pubmed | |
LHCGRSegaloff DL. Constitutive activity of the lutropin receptor and its allosteric modulation by receptor heterodimerization. Methods Enzymol. 2010;484:231-52. Pubmed | Kleinau G, Krause G. Thyrotropin and homologous glycoprotein hormone receptors: structural and functional aspects of extracellular signaling mechanisms. Endocr Rev. 2009 Apr;30(2):133-51. Pubmed | Caltabiano G, Campillo M, De Leener A, Smits G, Vassart G, Costagliola S, Pardo L. The specificity of binding of glycoprotein hormones to their receptors. Cell Mol Life Sci. 2008 Aug;65(16):2484-92 Pubmed | Puett D, Li Y, Demars G, Angelova K, Fanelli F. A functional transmembrane complex: The luteinizing hormone receptor with bound ligand and G protein Mol Cell Endocrinol. 2007 Jan 2;260-262:126-36. Pubmed | Jeoung M, Lee C, Ji I, Ji TH Trans-activation, cis-activation and signal selection of gonadotropin receptors. Mol Cell Endocrinol. 2007 Jan 2;260-262:137-43 Pubmed | Themmen, A. P N. Focus on Gonadotrophin Signalling An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms Reproduction (2005) 130 263-274 Link | Puett D, Li Y, Angelova K, Demars G, Meehan TP, Fanelli F, Narayan P Structure-function relationships of the luteinizing hormone receptor. Ann N Y Acad Sci. 2005 Dec;1061:41-54 Pubmed | Vassart G, Pardo L, Costagliola S A molecular dissection of the glycoprotein hormone receptors Trends Biochem Sci. 2004 Mar;29(3):119-26 Pubmed | Shenker A Activating mutations of the lutropin choriogonadotropin receptor in precocious puberty Receptors Channels, 2002;8(1):3-18 Pubmed | Ascoli M, Fanelli F, Segaloff DL The Lutropin/Choriogonadotropin Receptor, A 2002 Perspective Endocr Rev. 2002 Apr;23(2):141-74 Pubmed | Yi CS, Song YS, Ryu KS, Sohn J, Ji I, Ji TH Common and differential mechanisms of gonadotropin receptors Cell Mol Life Sci. 2002 Jun;59(6):932-40 Pubmed | Themmen APN, Huhtaniemi IT Mutations of Gonadotropin and Gonadotropin Receptors: Elucidating the Physiology and Pathophysiology of Pituitary-Gonadal Function Endocr Rev. 2000 Oct;21(5):551-83 Pubmed | Dufau ML The luteinizing hormone receptor Annu Rev Physiol. 1998;60:461-96 Pubmed | Kosugi S, Sugawa H, Mori T TSH receptor and LH receptor, 1996 Endocr J. 1996 Dec;43(6):595-604 Pubmed | |
Cysteine-box 1
Ji I, Lee C, Jeoung M, Koo Y, Sievert GA, Ji TH Trans-activation of mutant follicle-stimulating hormone receptors selectively generates only one of two hormone signals Mol Endocrinol. 2004 Apr;18(4):968-78 Pubmed | Piotrowska U, Adler G, Kilianski J Residues 34-39 in the thyrotropin receptor are not the target of autoantibodies from sera of patients with Graves' disease Endocr Res. 2004 Aug;30(3):431-41 Pubmed | Kleinau G, Jaschke H, Neumann S, Lattig J, Paschke R, Krause G Identification of a novel epitope in the thyroid-stimulating hormone receptor ectodomain acting as intramolecular signaling interface J Biol Chem. 2004 Dec 3;279(49):51590-600 Pubmed | Sohn J, Youn H, Jeoung M, Koo Y, Yi C, Ji I, Ji TH Orientation of follicle-stimulating hormone (FSH) subunits complexed with the FSH receptor. Beta subunit toward the N terminus of exodomain and alpha subunit to exoloop 3 J Biol Chem. 2003 Nov 28;278(48):47868-76 Pubmed | Zhang R, Buczko E, Dufau ML Requirement of cysteine residues in exons 1-6 of the extracellular domain of the luteinizing hormone receptor for gonadotropin binding J Biol Chem. 1996 Mar 8;271(10):5755-60 Pubmed | Gustavsson B, Eklof C, Westermark K, Westermark B, Heldin NE Functional analysis of a variant of the thyrotropin receptor gene in a family with Graves' disease Mol Cell Endocrinol 1995 Jun;111(2):167-73 Pubmed | Wadsworth HL, Russo D, Nagayama Y, Chazenbalk GD, Rapoport B Studies on the role of amino acids 38-45 in the expression of a functional thyrotropin receptor Mol Endocrinol 1992 Mar;6(3):394-8 Pubmed | |
LRRD / Hormone binding
Chen CR, McLachlan SM, Rapoport B. Thyrotropin (TSH) receptor residue E251 in the extracellular leucine-rich repeat domain is critical for linking TSH binding to receptor activation. Endocrinology. 2010 Apr;151(4):1940-7 Pubmed | Angelova K, de Jonge H, Granneman JC, Puett D, Bogerd J. Functional differences of invariant and highly conserved residues in the extracellular domain of the glycoprotein hormone receptors. J Biol Chem. 2010 Nov 5;285(45):34813-27 Pubmed | Chen CR, McLachlan SM, Rapoport B IDENTIFICATION OF KEY AMINO ACID RESIDUES IN A THYROTROPIN RECEPTOR MONOCLONAL ANTIBODY EPITOPE PROVIDES INSIGHT INTO ITS INVERSE AGONIST AND ANTAGONIST PROPERTIES. Endocrinology. 2008 Jul;149(7):3427-34 Pubmed | Caltabiano G, Campillo M, De Leener A, Smits G, Vassart G, Costagliola S, Pardo L. The specificity of binding of glycoprotein hormones to their receptors. Cell Mol Life Sci. 2008 Aug;65(16):2484-92 Pubmed | Royer J, Lefevre-Minisini A, Caltabiano G, Lacombe T, Malthiery Y, Savagner F, Pardo L, Rodien P. The cloned equine thyrotropin receptor is hypersensitive to human chorionic gonadotropin; identification of three residues in the extracellular domain involved in ligand specificity. Endocrinology. 2008 Oct;149(10):5088-96 Pubmed | Lin W, Bernard MP, Cao D, Myers RV, Kerrigan JE, Moyle WR Follitropin receptors contain cryptic ligand binding sites. Mol Cell Endocrinol. 2007 Jan 2;260-262:83-92 Pubmed | Fan QR, Hendrickson WA Assembly and structural characterization of an authentic complex between human follicle stimulating hormone and a hormone-binding ectodomain of its receptor. Mol Cell Endocrinol. 2007 Jan 2;260-262:73-82. Pubmed | Bogerd J Ligand-selective determinants in gonadotropin receptors Mol Cell Endocrinol. 2007 Jan 2;260-262:144-52 Pubmed | Sanders J, Bolton J, Sanders P, Jeffreys J, Nakatake N, Richards T, Evans M, Kiddie A, Summerhayes S, Roberts E, Miguel RN, Furmaniak J, Smith BR Effects of TSH receptor mutations on binding and biological activity of monoclonal antibodies and TSH. Thyroid. 2006 Dec;16(12):1195-206 Pubmed | Fan QR, Hendrickson WA Structure of human follicle-stimulating hormone in complex with its receptor Nature. 2005 Jan 20;433(7023):203-4 Pubmed | Galet C, Ascoli M The differential binding affinities of the luteinizing hormone (LH)/choriogonadotropin receptor for LH and choriogonadotropin are dictated by different extracellular domain residues Mol Endocrinol. 2005 May;19(5):1263-76 Pubmed | Fan QR, Hendrickson WA Structural biology of glycoprotein hormones and their receptors Endocrine. 2005 Apr;26(3):179-88 Pubmed | Dias JA. Endocrinology: fertility hormone in repose. Nature. 2005 Jan 20;433(7023):203-4 Pubmed | Gudermann T, Nurwakagari P, Ben-Menahem D Hormone binding to the follicle-stimulating hormone receptor--crystal clear! Exp Clin Endocrinol Diabetes. 2005 May;113(5):245-7 Pubmed | Matsushima N, Tachi N, Kuroki Y, Enkhbayar P, Osaki M, Kamiya M, Kretsinger RH Structural analysis of leucine-rich-repeat variants in proteins associated with human diseases Cell Mol Life Sci. 2005 Dec;62(23):2771-91 Pubmed | Kleinau G, Jaschke H, Neumann S, Lattig J, Paschke R, Krause G Identification of a novel epitope in the thyroid-stimulating hormone receptor ectodomain acting as intramolecular signaling interface J Biol Chem. 2004 Dec 3;279(49):51590-600 Pubmed | Vischer HF, Granneman JC, Noordam MJ, Mosselman S, Bogerd J Ligand selectivity of gonadotropin receptors. Role of the beta-strands of extracellular leucine-rich repeats 3 and 6 of the human luteinizing hormone receptor J Biol Chem. 2003 May 2;278(18):15505-13 Pubmed | Smits G, Campillo M, Govaerts C, Janssens V, Richter C, Vassart G, Pardo L, Costagliola S Glycoprotein hormone receptors: determinants in leucine-rich repeats responsible for ligand specificity EMBO J., 2003 Jun 2;22(11):2692-703S Pubmed | Sohn J, Youn H, Jeoung M, Koo Y, Yi C, Ji I, Ji TH Orientation of follicle-stimulating hormone (FSH) subunits complexed with the FSH receptor. Beta subunit toward the N terminus of exodomain and alpha subunit to exoloop 3 J Biol Chem. 2003 Nov 28;278(48):47868-76 Pubmed | Bhowmick N, Narayan P, Puett D Identification of ionizable amino acid residues on the extracellular domain of the lutropin receptor involved in ligand binding Endocrinology. 1999 Oct;140(10):4558-63 Pubmed | Hong S, Phang T, Ji I, Ji TH The amino-terminal region of the luteinizing hormone/choriogonadotropin receptor contacts both subunits of human choriogonadotropin. I. Mutational analysis J Biol Chem. 1998 May 29;273(22):13835-40 Pubmed | Bhowmick N, Huang J, Puett D, Isaacs NW, Lapthorn AJ Determination of residues important in hormone binding to the extracellular domain of the luteinizing hormone/chorionic gonadotropin receptor by site-directed mutagenesis and modeling. Mol Endocrinol. 1996 Sep;10(9):1147-59 Pubmed | Nagayama Y, Yamasaki H, Takeshita A, Kimura H, Ashizawa K, Yokoyama N, Yamashita S, Rapoport B, Nagataki S. Thyrotropin binding specificity for the thyrotropin receptor. J Endocrinol Invest. 1995 Apr;18(4):283-7 Pubmed | Moyle WR, Campbell RK, Myers RV, Bernard MP, Han Y, Wang X. Co-evolution of ligand-receptor pairs. Nature. 1994 Mar 17;368(6468):251-5 Pubmed | Nagayama Y, Wadsworth HL, Chazenbalk GD, Russo D, Seto P, Rapoport B. Thyrotropin-luteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyrotropin receptor function. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):902-5. Pubmed | Nagayama Y, Russo D, Wadsworth HL, Chazenbalk GD, Rapoport B. Eleven amino acids (Lys-201 to Lys-211) and 9 amino acids (Gly-222 to Leu-230) in the human thyrotropin receptor are involved in ligand binding. J Biol Chem. 1991 Aug 15;266(23):14926-30. Pubmed | |
Cysteine-box 2
Mueller S, Kleinau G, Szkudlinski MW, Jaeschke H, Krause G, Paschke R The superagonistic activity of bovine thyroid-stimulating hormone (TSH) and the human TR1401 TSH analog is determined by specific amino acids in the hinge region of the human TSH receptor J Biol Chem. 2009 Jun 12;284(24):16317-24. Epub 2009 Apr 22 Pubmed | Mizutori Y, Chen CR, McLachlan SM, Rapoport B. The thyrotropin receptor hinge region is not simply a scaffold for the leucine-rich domain but contributes to ligand binding and signal transduction. Mol Endocrinol. 2008 May;22(5):1171-82 Pubmed | Mueller S, Kleinau G, Jaeschke H, Paschke R, Krause G. Extended Hormone Binding Site of the Human Thyroid Stimulating Hormone Receptor: DISTINCTIVE ACIDIC RESIDUES IN THE HINGE REGION ARE INVOLVED IN BOVINE THYROID STIMULATING HORMONE BINDING AND RECEPTOR ACTIVATION. J Biol Chem. 2008 Jun 27;283(26):18048-55 Pubmed | Bruysters M, Verhoef-Post M, Themmen AP. Asp330 and Tyr331 in the C-terminal cysteine-rich region of the luteinizing hormone receptor are key residues in hormone-induced receptor activation. J Biol Chem. 2008 Sep 19;283(38):25821-8. Pubmed | Ho SC, Goh SS, Li S, Khoo DH, Paterson M Effects of mutations involving cysteine residues distal to the S281HCC motif at the C-terminus on the functional characteristics of a truncated ectodomain-only thyrotropin receptor anchored on glycosylphosphatidyl-inositol. Thyroid. 2008 Dec;18(12):1313-9 Pubmed | Jaeschke H, Neumann S, Kleinau G, Mueller S, Claus M, Krause G, Paschke R An aromatic environment in the vicinity of serine281 is a structural requirement for TSH receptor function Endocrinology. 2006 Apr;147(4):1753-60 Pubmed | Mueller S, Kleinau G, Jaeschke H, Neumann S, Krause G, Paschke R. Significance of ectodomain cysteine boxes 2 and 3 for the activation mechanism of the thyroid-stimulating hormone receptor. J Biol Chem. 2006 Oct 20;281(42):31638-46. Pubmed | Neumann S, Claus M, Paschke R Interactions between the extracellular domain and the extracellular loops as well as the 6th transmembrane domain are necessary for TSH receptor activation Eur J Endocrinol. 2005 Apr;152(4):625-34 Pubmed | Ho SC, Goh SS, Su Q, Khoo DH Cysteine 390 mutation of the TSH receptor modulates its ectodomain as an inverse agonist on the serpentine domain with decrease in basal constitutive activity Mol Cell Endocrinol. 2005 Dec 21;245(1-2):158-68 Pubmed | Kleinau G, Jaschke H, Neumann S, Lattig J, Paschke R, Krause G Identification of a novel epitope in the thyroid-stimulating hormone receptor ectodomain acting as intramolecular signaling interface J Biol Chem. 2004 Dec 3;279(49):51590-600 Pubmed | Nakabayashi K, Kudo M, Hsueh AJ, Maruo T Activation of the luteinizing hormone receptor in the extracellular domain Mol Cell Endocrinol. 2003 Apr 28;202(1-2):139-44 Pubmed | Nishi S, Nakabayashi K, Kobilka B, Hsueh AJ The ectodomain of the luteinizing hormone receptor interacts with exoloop 2 to constrain the transmembrane region: studies using chimeric human and fly receptors J Biol Chem. 2002 Feb 8;277(6):3958-64 Pubmed | Sangkuhl K, Schulz A, Schultz G, Schoneberg T Structural requirements for mutational lutropin/choriogonadotropin receptor activation J Biol Chem. 2002 Dec 6;277(49):47748-55 Pubmed | Ho SC, Van Sande J, Lefort A, Vassart G, Costagliola S Effects of mutations involving the highly conserved S281HCC motif in the extracellular domain of the thyrotropin (TSH) receptor on TSH binding and constitutive activity Endocrinology. 2001 Jul;142(7):2760-7 Pubmed | Zeng H, Phang T, Song YS, Ji I, Ji TH The role of the hinge region of the luteinizing hormone receptor in hormone interaction and signal generation J Biol Chem. 2001 Feb 2;276(5):3451-8 Pubmed | Nakabayashi K, Kudo M, Kobilka B, Hsueh AJ Activation of the luteinizing hormone receptor following substitution of Ser-277 with selective hydrophobic residues in the ectodomain hinge region J Biol Chem. 2000 Sep 29;275(39):30264-71 Pubmed | Bernard MP, Myers RV, Moyle WR Lutropins appear to contact two independent sites in the extracellular domain of their receptors. Biochem J. 1998 Nov 1;335 ( Pt 3):611-7 Pubmed | Duprez L, Parma J, Costagliola S, Hermans J, Van Sande J, Dumont JE, Vassart G Constitutive activation of the TSH receptor by spontaneous mutations affecting the N-terminal extracellular domain. FEBS Lett. 1997 Jun 16;409(3):469-74 Pubmed | Zhang R, Buczko E, Dufau ML Requirement of cysteine residues in exons 1-6 of the extracellular domain of the luteinizing hormone receptor for gonadotropin binding J Biol Chem. 1996 Mar 8;271(10):5755-60 Pubmed | Akamizu T, Inoue D, Kosugi S, Kohn LD, Mori T Further studies of amino acids (268-304) in thyrotropin (TSH)--lutropin/chorionic gonadotropin (LH/CG) receptor chimeras: cysteine-301 is important in TSH binding and receptor tertiary structure Thyroid. 1994 Spring;4(1):43-8 Pubmed | Nagayama Y, Rapoport B. Role of the carboxyl-terminal half of the extracellular domain of the human thyrotropin receptor in signal transduction. Endocrinology. 1992 Aug;131(2):548-52. Pubmed | |
LHCGR - Exon 10
Scammell JG, Funkhouser JD, Moyer FS, Gibson SV, Willis DL Molecular cloning of pituitary glycoprotein alpha-subunit and follicle stimulating hormone and chorionic gonadotropin beta-subunits from New World squirrel monkey and owl monkey Gen Comp Endocrinol. 2008 Feb 1;155(3):534-41 Pubmed | Gromoll J, Lahrmann L, Godmann M, Müller T, Michel C, Stamm S, Simoni M Genomic checkpoints for exon 10 usage in the luteinizing hormone receptor type 1 and type 2 Mol Endocrinol. 2007 Aug;21(8):1984-96 Pubmed | Michel C, Gromoll J, Chandolia R, Luetjens CM, Wistuba J, Simoni M LHR splicing variants and gene expression in the marmoset monkey Mol Cell Endocrinol. 2007 Dec 15;279(1-2):9-15 Pubmed | Muller T, Simoni M, Pekel E, Luetjens CM, Chandolia R, Amato F, Norman RJ, Gromoll J Chorionic gonadotrophin beta subunit mRNA but not luteinising hormone beta subunit mRNA is expressed in the pituitary of the common marmoset (Callithrix jacchus) J Mol Endocrinol. 2004 Feb;32(1):115-28 Pubmed | Muller T, Gromoll J, Simula AP, Norman R, Sandhowe-Klaverkamp R, Simoni M The carboxyterminal peptide of chorionic gonadotropin facilitates activation of the marmoset LH receptor Exp Clin Endocrinol Diabetes. 2004 Nov;112(10):574-9 Pubmed | Mueller T, Gromoll J, Simoni M Absence of exon 10 of the human luteinizing hormone (LH) receptor impairs LH, but not human chorionic gonadotropin action J Clin Endocrinol Metab. 2003 May;88(5):2242-9 Pubmed | Gromoll J, Wistuba J, Terwort N, Godmann M, Muller T, Simoni M A new subclass of the luteinizing hormone/chorionic gonadotropin receptor lacking exon 10 messenger RNA in the New World monkey (Platyrrhini) lineage Biol Reprod. 2003 Jul;69(1):75-80 Pubmed | Gromoll J, Eiholzer U, Nieschlag E, Simoni M Male hypogonadism caused by homozygous deletion of exon 10 of the luteinizing hormone (LH) receptor: differential action of human chorionic gonadotropin and LH J Clin Endocrinol Metab. 2000 Jun;85(6):2281-6 Pubmed | |
Glycosylation
Clouser CL, Menon KM N-linked glycosylation facilitates processing and cell surface expression of rat luteinizing hormone receptor. Mol Cell Endocrinol. 2005 May 12;235(1-2):11-9 Pubmed | Frenzel R, Krohn K, Eszlinger M, Tonjes A, Paschke R Sialylation of human thyrotropin receptor improves and prolongs its cell-surface expression. Mol Pharmacol. 2005 Oct;68(4):1106-13 Pubmed | Nagayama Y, Nishihara E, Namba H, Yamashita S, Niwa M Identification of the sites of asparagine-linked glycosylation on the human thyrotropin receptor and studies on their role in receptor function and expression J Pharmacol Exp Ther. 2000 Oct;295(1):404-9 Pubmed | Oda Y, Sanders J, Roberts S, Maruyama M, Kiddie A, Furmaniak J, Smith BR Analysis of carbohydrate residues on recombinant human thyrotropin receptor. J Clin Endocrinol Metab. 1999 Jun;84(6):2119-25 Pubmed | Davis DP, Rozell TG, Liu X, Segaloff DL The six N-linked carbohydrates of the lutropin/choriogonadotropin receptor are not absolutely required for correct folding, cell surface expression, hormone binding, or signal transduction Mol Endocrinol. 1997 May;11(5):550-62 Pubmed | Zhang R, Cai H, Fatima N, Buczko E, Dufau ML Functional glycosylation sites of the rat luteinizing hormone receptor required for ligand binding J Biol Chem. 1995 Sep 15;270(37):21722-8 Pubmed | Davis D, Liu X, Segaloff DL Identification of the sites of N-linked glycosylation on the follicle-stimulating hormone (FSH) receptor and assessment of their role in FSH receptor function Mol Endocrinol. 1995 Feb;9(2):159-70 Pubmed | Russo D, Chazenbalk GD, Nagayama Y, Wadsworth HL, Rapoport B Site-directed mutagenesis of the human thyrotropin receptor: role of asparagine-linked oligosaccharides in the expression of a functional receptor Mol Endocrinol. 1991 Jan;5(1):29-33 Pubmed | Zhang R, Tsai-Morris CH, Kitamura M, Buczko E, Dufau ML Changes in binding activity of luteinizing hormone receptors by site directed mutagenesis of potential glycosylation sites Biochem Biophys Res Commun. 1991 Dec 16;181(2):804-8 Pubmed | |
Cleavage and Shedding
Vu MT, Radu A, Ghinea N. The cleavage of Thyroid-Stimulating Hormone receptor is dependent on cell-cell contacts and regulates the hormonal stimulation of phospholipase C. J Cell Mol Med. 2009 Aug;13(8B):2253-60. Pubmed | Kaczur V, Puskas LG, Nagy ZU, Miled N, Rebai A, Juhasz F, Kupihar Z, Zvara A, Hackler L Jr, Farid NR Cleavage of the human thyrotropin receptor by ADAM10 is regulated by thyrotropin. J Mol Recognit. 2007 Sep-Oct;20(5):392-404 Pubmed | Chen CR, Chazenbalk GD, Wawrowsky KA, McLachlan SM, Rapoport B Evidence that human thyroid cells express uncleaved, single-chain thyrotropin receptors on their surface. Endocrinology. 2006 Jun;147(6):3107-13 Pubmed | Chazenbalk GD, Chen CR, McLachlan SM, Rapoport B Does thyrotropin cleave its cognate receptor? Endocrinology. 2004 Jan;145(1):4-10 Pubmed | Vassart G, Costagliola S A physiological role for the posttranslational cleavage of the thyrotropin receptor? Endocrinology. 2004 Jan;145(1):1-3 Pubmed | Latif R, Ando T, Davies TF Monomerization as a prerequisite for intramolecular cleavage and shedding of the thyrotropin receptor Endocrinology. 2004 Dec;145(12):5580-8 Pubmed | Chen CR, Chazenbalk GD, McLachlan SM, Rapoport B Targeted restoration of cleavage in a noncleaving thyrotropin receptor demonstrates that cleavage is insufficient to enhance ligand-independent activity Endocrinology. 2003 Apr;144(4):1324-30 Pubmed | Ciullo I, Latif R, Graves P, Davies TF Functional assessment of the thyrotropin receptor-beta subunit Endocrinology. 2003 Jul;144(7):3176-81 Pubmed | Quellari M, Desroches A, Beau I, Beaudeux E, Misrahi M Role of cleavage and shedding in human thyrotropin receptor function and trafficking Eur J Biochem. 2003 Sep;270(17):3486-97 Pubmed | Chen CR, Chazenbalk GD, McLachlan SM, Rapoport B Evidence that the C terminus of the A subunit suppresses thyrotropin receptor constitutive activity Endocrinology. 2003 Sep;144(9):3821-7 Pubmed | Chazenbalk GD, McLachlan SM, Chen CR, Rapoport B Insight into thyrotropin receptor cleavage by engineering the single polypeptide chain luteinizing hormone receptor into a cleaving, two subunit receptor Eur J Biochem. 2001 Apr;268(8):2261-9 Pubmed | Tanaka K, Chazenbalk GD, McLachlan SM, Rapoport B Evidence that cleavage of the thyrotropin receptor involves a "molecular ruler" mechanism: deletion of amino acid residues 305-320 causes a spatial shift in cleavage site 1 independent of amino acid motif Endocrinology. 2000 Oct;141(10):3573-7 Pubmed | de Bernard S, Misrahi M, Huet JC, Beau I, Desroches A, Loosfelt H, Pichon C, Pernollet JC, Milgrom E Sequential cleavage and excision of a segment of the thyrotropin receptor ectodomain J Biol Chem. 1999 Jan 1;274(1):101-7 Pubmed | Tanaka K, Chazenbalk GD, McLachlan SM, Rapoport B The shed thyrotropin receptor is primarily a carboxyl terminal truncated form of the A subunit, not the entire A subunit Mol Cell Endocrinol. 1999 Apr 25;150(1-2):113-9 Pubmed | Chazenbalk GD, Tanaka K, McLachlan SM, Rapoport B. On the functional importance of thyrotropin receptor intramolecular cleavage. Endocrinology. 1999 Oct;140(10):4516-20 Pubmed | Tanaka K, Chazenbalk GD, McLachlan SM, Rapoport B Thyrotropin receptor cleavage at site 1 does not involve a specific amino acid motif but instead depends on the presence of the unique, 50 amino acid insertion J Biol Chem. 1998 Jan 23;273(4):1959-63 Pubmed | Chazenbalk GD, Tanaka K, Nagayama Y, Kakinuma A, Jaume JC, McLachlan SM, Rapoport B Evidence that the thyrotropin receptor ectodomain contains not one, but two, cleavage sites Endocrinology. 1997 Jul;138(7):2893-9 Pubmed | Kakinuma A, Chazenbalk GD, Tanaka K, Nagayama Y, McLachlan SM, Rapoport B An N-linked glycosylation motif from the noncleaving luteinizing hormone receptor substituted for the homologous region (Gly367 to Glu369) of the thyrotropin receptor prevents cleavage at its second, downstream site J Biol Chem. 1997 Nov 7; 272(45): 28296-300 Pubmed | Misrahi M, Milgrom E Cleavage and shedding of the TSH receptor Eur J Endocrinol. 1997 Dec;137(6):599-602 Pubmed | Couet J, Sar S, Jolivet A, Hai MT, Milgrom E, Misrahi M Shedding of human thyrotropin receptor ectodomain. Involvement of a matrix metalloprotease J Biol Chem. 1996 Feb 23;271(8):4545-52 Pubmed | Van Sande J, Massart C, Costagliola S, Allgeier A, Cetani F, Vassart G, Dumont JE Specific activation of the thyrotropin receptor by trypsin Mol Cell Endocrinol. 1996 May 31;119(2):161-8 Pubmed | Couet J, de Bernard S, Loosfelt H, Saunier B, Milgrom E, Misrahi M Cell surface protein disulfide-isomerase is involved in the shedding of human thyrotropin receptor ectodomain Biochemistry. 1996 Nov 26;35(47):14800-5 Pubmed | Loosfelt H, Pichon C, Jolivet A, Misrahi M, Caillou B, Jamous M, Vannier B, Milgrom E Two-subunit structure of the human thyrotropin receptor Proc Natl Acad Sci U S A. 1992 May 1;89(9):3765-9 Pubmed | |
Cysteine-box 2/3 linker region
Hamidi S, Chen CR, Mizutori-Sasai Y, McLachlan SM, Rapoport B. Relationship between Thyrotropin Receptor Hinge Region Proteolytic Posttranslational Modification and Receptor Physiological Function. Mol Endocrinol. 2011 Jan;25(1):184-94. Pubmed | Mueller S, Kleinau G, Szkudlinski MW, Jaeschke H, Krause G, Paschke R The superagonistic activity of bovine thyroid-stimulating hormone (TSH) and the human TR1401 TSH analog is determined by specific amino acids in the hinge region of the human TSH receptor J Biol Chem. 2009 Jun 12;284(24):16317-24. Epub 2009 Apr 22 Pubmed | Agrawal G, Dighe RR Critical involvement of the hinge region of the follicle-stimulating hormone receptor in the activation of the receptor. J Biol Chem. 2009 Jan 30;284(5):2636-47. Epub 2008 Nov 24. Pubmed | Mizutori Y, Chen CR, McLachlan SM, Rapoport B. The thyrotropin receptor hinge region is not simply a scaffold for the leucine-rich domain but contributes to ligand binding and signal transduction. Mol Endocrinol. 2008 May;22(5):1171-82 Pubmed | Mueller S, Kleinau G, Jaeschke H, Paschke R, Krause G. Extended Hormone Binding Site of the Human Thyroid Stimulating Hormone Receptor: DISTINCTIVE ACIDIC RESIDUES IN THE HINGE REGION ARE INVOLVED IN BOVINE THYROID STIMULATING HORMONE BINDING AND RECEPTOR ACTIVATION. J Biol Chem. 2008 Jun 27;283(26):18048-55 Pubmed | Bruysters M, Verhoef-Post M, Themmen AP. Asp330 and Tyr331 in the C-terminal cysteine-rich region of the luteinizing hormone receptor are key residues in hormone-induced receptor activation. J Biol Chem. 2008 Sep 19;283(38):25821-8. Pubmed | Bonomi M, Busnelli M, Persani L, Vassart G, Costagliola S. Structural differences in the "hinge region" of the glycoprotein-hormone receptors: evidences from the sulfated tyrosine residues. Mol Endocrinol. 2006 Dec;20(12):3351-63 Pubmed | Costagliola S, Panneels V, Bonomi M, Koch J, Many MC, Smits G, Vassart G Tyrosine sulfation is required for agonist recognition by glycoprotein hormone receptors EMBO J. 2002 Feb 15;21(4):504-13 Pubmed | Russo D, Betterle C, Arturi F, Chiefari E, Girelli ME, Filetti S A novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH. J Clin Endocrinol Metab. 2000 Nov;85(11):4238-42 Pubmed | Van Sande J, Massart C, Costagliola S, Allgeier A, Cetani F, Vassart G, Dumont JE Specific activation of the thyrotropin receptor by trypsin Mol Cell Endocrinol. 1996 May 31;119(2):161-8 Pubmed | Kosugi S, Ban T, Akamizu T, Kohn LD Site-directed mutagenesis of a portion of the extracellular domain of the rat thyrotropin receptor important in autoimmune thyroid disease and nonhomologous with gonadotropin receptors. Relationship of functional and immunogenic domains J Biol Chem. 1991 Oct 15;266(29):19413-8 Pubmed | |
Cysteine-box 3
Mizutori Y, Chen CR, McLachlan SM, Rapoport B. The thyrotropin receptor hinge region is not simply a scaffold for the leucine-rich domain but contributes to ligand binding and signal transduction. Mol Endocrinol. 2008 May;22(5):1171-82 Pubmed | Mueller S, Kleinau G, Jaeschke H, Paschke R, Krause G. Extended Hormone Binding Site of the Human Thyroid Stimulating Hormone Receptor: DISTINCTIVE ACIDIC RESIDUES IN THE HINGE REGION ARE INVOLVED IN BOVINE THYROID STIMULATING HORMONE BINDING AND RECEPTOR ACTIVATION. J Biol Chem. 2008 Jun 27;283(26):18048-55 Pubmed | Bruysters M, Verhoef-Post M, Themmen AP. Asp330 and Tyr331 in the C-terminal cysteine-rich region of the luteinizing hormone receptor are key residues in hormone-induced receptor activation. J Biol Chem. 2008 Sep 19;283(38):25821-8. Pubmed | Mueller S, Kleinau G, Jaeschke H, Neumann S, Krause G, Paschke R. Significance of ectodomain cysteine boxes 2 and 3 for the activation mechanism of the thyroid-stimulating hormone receptor. J Biol Chem. 2006 Oct 20;281(42):31638-46. Pubmed | Ho SC, Goh SS, Su Q, Khoo DH Cysteine 390 mutation of the TSH receptor modulates its ectodomain as an inverse agonist on the serpentine domain with decrease in basal constitutive activity Mol Cell Endocrinol. 2005 Dec 21;245(1-2):158-68 Pubmed | Kleinau G, Jaschke H, Neumann S, Lattig J, Paschke R, Krause G Identification of a novel epitope in the thyroid-stimulating hormone receptor ectodomain acting as intramolecular signaling interface J Biol Chem. 2004 Dec 3;279(49):51590-600 Pubmed | Alvarez CA, Narayan P, Huang J, Puett D Characterization of a region of the lutropin receptor extracellular domain near transmembrane helix 1 that is important in ligand-mediated signaling Endocrinology. 1999 Apr;140(4):1775-82 Pubmed | Bernard MP, Myers RV, Moyle WR Lutropins appear to contact two independent sites in the extracellular domain of their receptors. Biochem J. 1998 Nov 1;335 ( Pt 3):611-7 Pubmed | Zhang R, Buczko E, Dufau ML Requirement of cysteine residues in exons 1-6 of the extracellular domain of the luteinizing hormone receptor for gonadotropin binding J Biol Chem. 1996 Mar 8;271(10):5755-60 Pubmed | Nagayama Y, Rapoport B. Role of the carboxyl-terminal half of the extracellular domain of the human thyrotropin receptor in signal transduction. Endocrinology. 1992 Aug;131(2):548-52. Pubmed | Kosugi S, Ban T, Akamizu T, Kohn LD Site-directed mutagenesis of a portion of the extracellular domain of the rat thyrotropin receptor important in autoimmune thyroid disease and nonhomologous with gonadotropin receptors. Relationship of functional and immunogenic domains J Biol Chem. 1991 Oct 15;266(29):19413-8 Pubmed | |
Promiscuous Hormone Binding
De Leener A, Caltabiano G, Erkan S, Idil M, Vassart G, Pardo L, Costagliola S. Identification of the first germline mutation in the extracellular domain of the follitropin receptor responsible for spontaneous ovarian hyperstimulation syndrome. Hum Mutat. 2008 Jan;29(1):91-8. Pubmed | Vischer HF, Granneman JC, Koelink PJ, Marques RB, Bogerd J. Identification of a luteinizing hormone-selective determinant in the exodomain of a follicle-stimulating hormone receptor. Gen Comp Endocrinol. 2008 May 1;156(3):490-8 Pubmed | Royer J, Lefevre-Minisini A, Caltabiano G, Lacombe T, Malthiery Y, Savagner F, Pardo L, Rodien P. The cloned equine thyrotropin receptor is hypersensitive to human chorionic gonadotropin; identification of three residues in the extracellular domain involved in ligand specificity. Endocrinology. 2008 Oct;149(10):5088-96 Pubmed | De Leener A, Montanelli L, Van Durme J, Chae H, Smits G, Vassart G, Costagliola S Presence and absence of FSH receptor mutations provide some insights to spontaneous ovarian hyperstimulation syndrome physiopathology. J Clin Endocrinol Metab. 2006 Feb;91(2):555-62 Pubmed | Bogerd J, Granneman JC, Schulz RW, Vischer HF Fish FSH receptors bind LH: How to make the human FSH receptor to be more fishy? Gen Comp Endocrinol. 2005 May 15;142(1-2):34-43 Pubmed | Costagliola S, Urizar E, Mendive F, Vassart G Specificity and promiscuity of gonadotropin receptors Reproduction. 2005 Sep;130(3):275-81 Pubmed | Montanelli L, Van Durme JJ, Smits G, Bonomi M, Rodien P, Devor EJ, Moffat-Wilson K, Pardo L, Vassart G, Costagliola S Modulation of ligand selectivity associated with activation of the transmembrane region of the human follitropin receptor Mol Endocrinol. 2004 Aug;18(8):2061-73 Pubmed | Montanelli L, Delbaere A, Di Carlo C, Nappi C, Smits G, Vassart G, Costagliola S A mutation in the follicle-stimulating hormone receptor as a cause of familial spontaneous ovarian hyperstimulation syndrome J Clin Endocrinol Metab. 2004 Apr;89(4):1255-8 Pubmed | Vasseur C, Rodien P, Beau I, Desroches A, Gerard C, de Poncheville L, Chaplot S, Savagner F, Croue A, Mathieu E, Lahlou N, Descamps P, Misrahi M A chorionic gonadotropin-sensitive mutation in the follicle-stimulating hormone receptor as a cause of familial gestational spontaneous ovarian hyperstimulation syndrome N Engl J Med. 2003 Aug 21;349(8):753-9. Pubmed | Smits G, Govaerts C, Nubourgh I, Pardo L, Vassart G, Costagliola S Lysine 183 and glutamic acid 157 of the TSH receptor: two interacting residues with a key role in determining specificity toward TSH and human CG Mol Endocrinol. 2002 Apr;16(4):722-35 Pubmed | |
Superactive GPH analogues
Szkudlinski MW Past, presence and future of thyroid-stimulating hormone (TSH) superactive analogs Cancer Treat Res. 2004;122:345-56 Pubmed | Leitolf H, Tong KP, Grossmann M, Weintraub BD, Szkudlinski MW Bioengineering of human thyrotropin superactive analogs by site-directed "lysine-scanning" mutagenesis. Cooperative effects between peripheral loops J Biol Chem. 2000 Sep 1;275(35):27457-65 Pubmed | Grossmann M, Leitolf H, Weintraub BD, Szkudlinski MW A rational design strategy for protein hormone superagonists Nat Biotechnol. 1998 Sep;16(9):871-5 Pubmed | Szkudlinski MW, Teh NG, Grossmann M, Tropea JE, Weintraub BD Engineering human glycoprotein hormone superactive analogues Nat Biotechnol. 1996 Oct;14(10):1257-63 Pubmed | |
Thyrostimulin
Sun SC, Hsu PJ, Wu FJ, Li SH, Lu CH, Luo CW Thyrostimulin, but not thyroid-stimulating hormone (TSH), acts as a paracrine regulator to activate the TSH receptor in mammalian ovary. J Biol Chem. 2010 Feb 5;285(6):3758-65 Pubmed | van Zeijl CJ, Surovtseva OV, Wiersinga WM, Boelen A, Fliers E. Transient hypothyroxinemia in juvenile glycoprotein hormone subunit B5 knock-out mice. Mol Cell Endocrinol. 2010 Jun 10;321(2):231-8 Pubmed | Sellami A, Agricola HJ, Veenstra JA. Neuroendocrine cells in Drosophila melanogaster producing GPA2/GPB5, a hormone with homology to LH, FSH and TSH. Gen Comp Endocrinol. 2010 Nov 28. [Epub ahead of print] Pubmed | Alvarez E, Cahoreau C, Combarnous Y. Comparative structure analyses of cystine knot-containing molecules with eight aminoacyl ring including glycoprotein hormones (GPH) alpha and beta subunits and GPH-related A2 (GPA2) and B5 (GPB5) molecules. Reprod Biol Endocrinol. 2009 Aug 31;7:90 Pubmed | Okajima Y, Nagasaki H, Suzuki C, Suga H, Ozaki N, Arima H, Hamada Y, Civelli O, Oiso Y Biochemical roles of the oligosaccharide chains in thyrostimulin, a heterodimeric hormone of glycoprotein hormone subunits alpha 2 (GPA2) and beta 5 (GPB5) Regul Pept. 2008 Jun 5;148(1-3):62-7 Pubmed | Lantz M, Vondrichova T, Capretz A, Nilsson E, Frenander C, Bondeson AG, Ridderstrale M, Aberg M, Asman P, Groop L, Hallengren B Thyrostimulin (a TSH-like Hormone) Expression in Orbital and Thyroid Tissue Thyroid. 2007 Feb;17(2):113-8 Pubmed | Okada SL, Ellsworth JL, Durnam DM, Haugen HS, Holloway JL, Kelley ML, Lewis KE, Ren H, Sheppard PO, Storey HM, Waggie KS, Wolf AC, Yao LY, Webster PJ A glycoprotein hormone expressed in corticotrophs exhibits unique binding properties on thyroid-stimulating hormone receptor Mol Endocrinol. 2006 Feb;20(2):414-25 Pubmed | Nagasaki H, Wang Z, Jackson VR, Lin S, Nothacker HP, Civelli O Differential expression of the thyrostimulin subunits, glycoprotein alpha2 and beta5 in the rat pituitary J Mol Endocrinol. 2006 Aug;37(1):39-50 Pubmed | Sudo S, Kuwabara Y, Park JI, Hsu SY, Hsueh AJ Heterodimeric fly glycoprotein hormone-alpha2 (GPA2) and glycoprotein hormone-beta5 (GPB5) activate fly leucine-rich repeat-containing G protein-coupled receptor-1 (DLGR1) and stimulation of human thyrotropin receptors by chimeric fly GPA2 and human GPB5 Endocrinology. 2005 Aug;146(8):3596-604 Pubmed | Park JI, Semyonov J, Chang CL, Hsu SY Conservation of the heterodimeric glycoprotein hormone subunit family proteins and the LGR signaling system from nematodes to humans Endocrine. 2005 Apr;26(3):267-76 Pubmed | Li C, Hirooka Y, Habu S, Takagi J, Gotoh M, Nogimori T Distribution of thyrostimulin in the rat: an immunohistochemical study Endocr Regul. 2004 Dec;38(4):131-42 Pubmed | Nakabayashi K, Matsumi H, Bhalla A, Bae J, Mosselman S, Hsu SY, Hsueh AJ Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits, activates the thyroid-stimulating hormone receptor J Clin Invest. 2002 Jun;109(11):1445-52 Pubmed | Hsu SY, Nakabayashi K, Bhalla A Evolution of glycoprotein hormone subunit genes in bilateral metazoa: identification of two novel human glycoprotein hormone subunit family genes, GPA2 and GPB5 Mol Endocrinol. 2002 Jul;16(7):1538-51 Pubmed | |
Interplay Extracellular Domain/Serpentine domain (SD)
Hamidi S, Chen CR, Mizutori-Sasai Y, McLachlan SM, Rapoport B. Relationship between Thyrotropin Receptor Hinge Region Proteolytic Posttranslational Modification and Receptor Physiological Function. Mol Endocrinol. 2011 Jan;25(1):184-94. Pubmed | Chen CR, McLachlan SM, Rapoport B Evidence that the thyroid-stimulating hormone (TSH) receptor transmembrane domain influences kinetics of TSH binding to the receptor ectodomain. J Biol Chem. 2011 Feb 25;286(8):6219-24 Pubmed | Nurwakagari P, Breit A, Hess C, Salman-Livny H, Ben-Menahem D, Gudermann T A conformational contribution of the luteinizing hormone-receptor ectodomain to receptor activation. J Mol Endocrinol. 2007 Feb;38(1-2):259-75 Pubmed | Neumann S, Claus M, Paschke R Interactions between the extracellular domain and the extracellular loops as well as the 6th transmembrane domain are necessary for TSH receptor activation Eur J Endocrinol. 2005 Apr;152(4):625-34 Pubmed | Karges B, Gidenne S, Aumas C, Haddad F, Kelly PA, Milgrom E, de Roux N Zero-length cross-linking reveals that tight interactions between the extracellular and transmembrane domains of the LH receptor persist during receptor activation Mol Endocrinol. 2005 Aug;19(8):2086-98 Pubmed | Vlaeminck-Guillem V, Ho SC, Rodien P, Vassart G, Costagliola S Activation of the cAMP pathway by the TSH receptor involves switching of the ectodomain from a tethered inverse agonist to an agonist Mol Endocrinol. 2002 Apr;16(4):736-46 Pubmed | Jaquette J, Segaloff DL Constitutive activation of the LH receptor is associated with an alteration in the conformation of the ectodomain Mol Cell Endocrinol. 2002 Aug 30;194(1-2):211-5 Pubmed | Sangkuhl K, Schulz A, Schultz G, Schoneberg T Structural requirements for mutational lutropin/choriogonadotropin receptor activation J Biol Chem. 2002 Dec 6;277(49):47748-55 Pubmed | Zhang M, Tong KP, Fremont V, Chen J, Narayan P, Puett D, Weintraub BD, Szkudlinski MW The extracellular domain suppresses constitutive activity of the transmembrane domain of the human TSH receptor: implications for hormone-receptor interaction and antagonist design Endocrinology. 2000 Sep;141(9):3514-7 Pubmed | Zhang ML, Sugawa H, Kosugi S, Mori T Constitutive activation of the thyrotropin receptor by deletion of a portion of the extracellular domain Biochem Biophys Res Commun. 1995 Jun 6;211(1):205-10 Pubmed | |
Transmembrane Helices 1-7 (TMHs 1-7)
Urizar E, Claeysen S, Deupi X, Govaerts C, Costagliola S, Vassart G, Pardo L An Activation Switch in the Rhodopsin Family of G Protein-coupled Receptors: THE THYROTROPIN RECEPTOR J Biol Chem. 2005 Apr 29;280(17):17135-41 Pubmed | Karges B, Krause G, Homoki J, Debatin KM, de Roux N, Karges W. TSH receptor mutation V509A causes familial hyperthyroidism by release of interhelical constraints between transmembrane helices TMH3 and TMH5. J Endocrinol. 2005 Aug;186(2):377-85 Pubmed | Fanelli F, Verhoef-Post M, Timmerman M, Zeilemaker A, Martens JW, Themmen AP Insight into mutation-induced activation of the luteinizing hormone receptor: molecular simulations predict the functional behavior of engineered mutants at M398 Mol Endocrinol. 2004 Jun;18(6):1499-508 Pubmed | Claeysen S, Govaerts C, Lefort A, Van Sande J, Costagliola S, Pardo L, Vassart G A conserved Asn in TM7 of the thyrotropin receptor is a common requirement for activation by both mutations and its natural agonist FEBS Lett. 2002 Apr 24;517(1-3):195-200 Pubmed | Tao YX, Mizrachi D, Segaloff DL Chimeras of the rat and human FSH receptors (FSHRs) identify residues that permit or suppress transmembrane 6 mutation-induced constitutive activation of the FSHR via rearrangements of hydrophobic interactions between helices 6 and 7 Mol Endocrinol. 2002 Aug;16(8):1881-92 Pubmed | Angelova K, Fanelli F, Puett D A model for constitutive lutropin receptor activation based on molecular simulation and engineered mutations in transmembrane helices 6 and 7 J Biol Chem. 2002 Aug 30;277(35):32202-13 Pubmed | Govaerts C, Lefort A, Costagliola S, Wodak SJ, Ballesteros JA, Van Sande J, Pardo L, Vassart G A conserved Asn in transmembrane helix 7 is an on/off switch in the activation of the thyrotropin receptor J Biol Chem. 2001 Jun 22;276(25):22991-9 Pubmed | Neumann S, Krause G, Chey S, Paschke R A free carboxylate oxygen in the side chain of position 674 in transmembrane domain 7 is necessary for TSH receptor activation Mol Endocrinol. 2001 Aug;15(8):1294-305 Pubmed | Angelova K, Narayan P, Simon JP, Puett D Functional role of transmembrane helix 7 in the activation of the heptahelical lutropin receptor Mol Endocrinol. 2000 Apr;14(4):459-71 Pubmed | Schulz A, Bruns K, Henklein P, Krause G, Schubert M, Gudermann T, Wray V, Schultz G, Schoneberg T Requirement of specific intrahelical interactions for stabilizing the inactive conformation of glycoprotein hormone receptors J Biol Chem. 2000 Dec 1;275(48):37860-9 Pubmed | Alvarez CA, Narayan P, Huang J, Puett D Characterization of a region of the lutropin receptor extracellular domain near transmembrane helix 1 that is important in ligand-mediated signaling Endocrinology. 1999 Apr;140(4):1775-82 Pubmed | Abell AN, McCormick DJ, Segaloff DL Certain activating mutations within helix 6 of the human luteinizing hormone receptor may be explained by alterations that allow transmembrane regions to activate Gs Mol Endocrinol. 1998 Dec;12(12):1857-69 Pubmed | Kosugi S, Mori T, Shenker A An anionic residue at position 564 is important for maintaining the inactive conformation of the human lutropin/choriogonadotropin receptor Mol Pharmacol. 1998 May;53(5):894-901 Pubmed | Biebermann H, Schoneberg T, Schulz A, Krause G, Gruters A, Schultz G, Gudermann T A conserved tyrosine residue (Y601) in transmembrane domain 5 of the human thyrotropin receptor serves as a molecular switch to determine G-protein coupling FASEB J. 1998 Nov;12(14):1461-71 Pubmed | Min KS, Liu X, Fabritz J, Jaquette J, Abell AN, Ascoli M Mutations that induce constitutive activation and mutations that impair signal transduction modulate the basal and/or agonist-stimulated internalization of the Lutropin/Choriogonadotropin receptor J Biol Chem. 1998 Dec 25;273(52):34911-9 Pubmed | Kosugi S, Mori T, Shenker A The role of Asp578 in maintaining the inactive conformation of the human lutropin/choriogonadotropin receptor J Biol Chem. 1996 Dec 13;271(50):31813-7 Pubmed | Fernandez LM, Puett D Identification of amino acid residues in transmembrane helices VI and VII of the lutropin/choriogonadotropin receptor involved in signaling Biochemistry. 1996 Apr 2;35(13):3986-93 Pubmed | Kudo M, Osuga Y, Kobilka BK, Hsueh AJ Transmembrane regions V and VI of the human luteinizing hormone receptor are required for constitutive activation by a mutation in the third intracellular loop J Biol Chem. 1996 Sep 13;271(37):22470-8 Pubmed | Kosugi S, Shenker A, Mori T Constitutive activation of cyclic AMP but not phosphatidylinositol signaling caused by four mutations in the 6th transmembrane helix of the human thyrotropin receptor FEBS Lett. 1994 Dec 19;356(2-3):291-4 Pubmed | Shenker A, Laue L, Kosugi S, Merendino JJ Jr, Minegishi T, Cutler GB Jr A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty Nature. 1993 Oct 14;365(6447):652-4 Pubmed | |
ECL1
Kleinau G, Jaeschke H, Mueller S, Raaka BM, Neumann S, Paschke R, Krause G Evidence for cooperative signal triggering at the extracellular loops of the TSH receptor FASEB J. 2008 Aug;22(8):2798-808 Pubmed | Jaeschke H, Neumann S, Kleinau G, Mueller S, Claus M, Krause G, Paschke R An aromatic environment in the vicinity of serine281 is a structural requirement for TSH receptor function Endocrinology. 2006 Apr;147(4):1753-60 Pubmed | Ji I, Ji TH Differential roles of exoloop 1 of the human follicle-stimulating hormone receptor in hormone binding and receptor activation J Biol Chem. 1995 Jul 7;270(27):15970-3 Pubmed | Rozzell TG, Wang H, Liu X, Segaloff DL Intracellular retention of mutant gonadotropin receptors results in loss of hormone binding activity of the follitropin receptor but not of the lutropin/choriogonadotropin receptor Mol Endocrinol. 1995 Dec;9(12):1727-36 Pubmed | Parma J, Van Sande J, Swillens S, Tonacchera M, Dumont J, Vassart G Somatic mutations causing constitutive activity of the thyrotropin receptor are the major cause of hyperfunctioning thyroid adenomas: identification of additional mutations activating both the cyclic adenosine 3',5'-monophosphate and inositol phosphate-Ca2+ cascades Mol Endocrinol. 1995 Jun;9(6):725-33 Pubmed | |
ECL2
Kleinau G, Jaeschke H, Mueller S, Raaka BM, Neumann S, Paschke R, Krause G Evidence for cooperative signal triggering at the extracellular loops of the TSH receptor FASEB J. 2008 Aug;22(8):2798-808 Pubmed | Kleinau G, Claus M, Jaeschke H, Mueller S, Neumann S, Paschke R, Krause G. Contacts between extracellular loop two and transmembrane helix six determine basal activity of the thyroid stimulating hormone receptor. J Biol Chem. 2007 Jan 5;282(1):518-25 Pubmed | Nishi S, Nakabayashi K, Kobilka B, Hsueh AJ The ectodomain of the luteinizing hormone receptor interacts with exoloop 2 to constrain the transmembrane region: studies using chimeric human and fly receptors J Biol Chem. 2002 Feb 8;277(6):3958-64 Pubmed | Li S, Liu X, Min L, Ascoli M Mutations of the second extracellular loop of the human lutropin receptor emphasize the importance of receptor activation and de-emphasize the importance of receptor phosphorylation in agonist-induced internalization J Biol Chem. 2001 Mar 16;276(11):7968-73 Pubmed | Ryu K, Lee H, Kim S, Beauchamp J, Tung CS, Isaacs NW, Ji I, Ji TH Modulation of high affinity hormone binding. Human choriogonadotropin binding to the exodomain of the receptor is influenced by exoloop 2 of the receptor J Biol Chem. 1998 Mar 13;273(11):6285-91 Pubmed | Couture L, Remy JJ, Rabesona H, Troalen F, Pajot-Augy E, Bozon V, Haertle T, Bidart JM, Salesse R A defined epitope on the human choriogonadotropin alpha-subunit interacts with the second extracellular loop of the transmembrane domain of the lutropin/choriogonadotropin receptor Eur J Biochem. 1996 Oct 15;241(2):627-32 Pubmed | |
ECL3
Kleinau G, Jaeschke H, Mueller S, Raaka BM, Neumann S, Paschke R, Krause G Evidence for cooperative signal triggering at the extracellular loops of the TSH receptor FASEB J. 2008 Aug;22(8):2798-808 Pubmed | Claus M, Jaeschke H, Kleinau G, Neumann S, Krause G, Paschke R A hydrophobic cluster in the center of the third extracellular loop is important for thyrotropin receptor signaling Endocrinology. 2005 Dec;146(12):5197-203 Pubmed | Sohn J, Youn H, Jeoung M, Koo Y, Yi C, Ji I, Ji TH Orientation of follicle-stimulating hormone (FSH) subunits complexed with the FSH receptor. Beta subunit toward the N terminus of exodomain and alpha subunit to exoloop 3 J Biol Chem. 2003 Nov 28;278(48):47868-76 Pubmed | Sohn J, Ryu K, Sievert G, Jeoung M, Ji I, Ji TH Follicle-stimulating hormone interacts with exoloop 3 of the receptor J Biol Chem. 2002 Dec 20;277(51):50165-75 Pubmed | Ryu K, Gilchrist RL, Tung CS, Ji I, Ji TH High affinity hormone binding to the extracellular N-terminal exodomain of the follicle-stimulating hormone receptor is critically modulated by exoloop 3 J Biol Chem. 1998 Oct 30;273(44):28953-8 Pubmed | Fernandez LM, Puett D Lys583 in the third extracellular loop of the lutropin/choriogonadotropin receptor is critical for signaling J Biol Chem. 1996 Jan 12;271(2):925-30 Pubmed | Gilchrist RL, Ryu KS, Ji I, Ji TH The luteinizing hormone/chorionic gonadotropin receptor has distinct transmembrane conductors for cAMP and inositol phosphate signals J Biol Chem. 1996 Aug 9;271(32):19283-7 Pubmed | Ryu KS, Gilchrist RL, Ji I, Kim SJ, Ji TH Exoloop 3 of the luteinizing hormone/choriogonadotropin receptor. Lys583 is essential and irreplaceable for human choriogonadotropin (hCG)-dependent receptor activation but not for high affinity hCG binding J Biol Chem. 1996 Mar 29;271(13):7301-4 Pubmed | Kosugi S, Mori T The third exoplasmic loop of the thyrotropin receptor is partially involved in signal transduction FEBS Lett. 1994 Jul 25;349(1):89-92 Pubmed | |
ICL1
Kleinau G, Jaeschke H, Worth CL, Mueller S, Gonzalez J, Paschke R, Krause G. Principles and determinants of G-protein coupling by the rhodopsin-like thyrotropin receptor. PLoS One. 2010 Mar 18;5(3):e9745 Pubmed | Kosugi S, Mori T The first cytoplasmic loop of the thyrotropin receptor is important for phosphoinositide signaling but not for agonist-induced adenylate cyclase activation FEBS Lett. 1994 Mar 21;341(2-3):162-6 Pubmed | Chazenbalk GD, Nagayama Y, Russo D, Wadsworth HL, Rapoport B Functional analysis of the cytoplasmic domains of the human thyrotropin receptor by site-directed mutagenesis J Biol Chem. 1990 Dec 5;265(34):20970-5 Pubmed | |
ICL2
Kleinau G, Jaeschke H, Worth CL, Mueller S, Gonzalez J, Paschke R, Krause G. Principles and determinants of G-protein coupling by the rhodopsin-like thyrotropin receptor. PLoS One. 2010 Mar 18;5(3):e9745 Pubmed | Angelova K, Fanelli F, Puett D Contributions of intracellular loops 2 and 3 of the lutropin receptor in gs coupling Mol Endocrinol. 2008 Jan;22(1):126-38 Pubmed | Feng X, Mueller T, Mizrachi D, Fanelli F, Segaloff DL An intracellular loop (IL2) residue confers different basal constitutive activities to the human lutropin receptor and human thyrotropin receptor through structural communication between IL2 and helix 6, via helix 3 Endocrinology. 2008 Apr;149(4):1705-17 Pubmed | Ulloa-Aguirre A, Uribe A, Zariñán T, Bustos-Jaimes I, Pérez-Solis MA, Dias JA Role of the intracellular domains of the human FSH receptor in G(alphaS) protein coupling and receptor expression Mol Cell Endocrinol. 2007 Jan 2;260-262:153-62 Pubmed | Neumann S, Krause G, Claus M, Paschke R Structural determinants for g protein activation and selectivity in the second intracellular loop of the thyrotropin receptor Endocrinology. 2005 Jan;146(1):477-85 Pubmed | Timossi C, Maldonado D, Vizcaino A, Lindau-Shepard B, Conn PM, Ulloa-Aguirre A Structural determinants in the second intracellular loop of the human follicle-stimulating hormone receptor are involved in G(s) protein activation Mol Cell Endocrinol. 2002 Mar 28;189(1-2):157-68 Pubmed | Fernandez LM, Puett D Evidence for an important functional role of intracellular loop II of the lutropin receptor Mol Cell Endocrinol. 1997 Apr 4;128(1-2):161-9 Pubmed | Kosugi S, Kohn LD, Akamizu T, Mori T The middle portion in the second cytoplasmic loop of the thyrotropin receptor plays a crucial role in adenylate cyclase activation Mol Endocrinol. 1994 Apr;8(4):498-509 Pubmed | Wang Z, Wang H, Ascoli M Mutation of a highly conserved acidic residue present in the second intracellular loop of G-protein-coupled receptors does not impair hormone binding or signal transduction of the luteinizing hormone/chorionic gonadotropin receptor Mol Endocrinol. 1993 Jan;7(1):85-93 Pubmed | Chazenbalk GD, Nagayama Y, Russo D, Wadsworth HL, Rapoport B Functional analysis of the cytoplasmic domains of the human thyrotropin receptor by site-directed mutagenesis J Biol Chem. 1990 Dec 5;265(34):20970-5 Pubmed | |
ICL3
Kleinau G, Jaeschke H, Worth CL, Mueller S, Gonzalez J, Paschke R, Krause G. Principles and determinants of G-protein coupling by the rhodopsin-like thyrotropin receptor. PLoS One. 2010 Mar 18;5(3):e9745 Pubmed | Angelova K, Fanelli F, Puett D Contributions of intracellular loops 2 and 3 of the lutropin receptor in gs coupling Mol Endocrinol. 2008 Jan;22(1):126-38 Pubmed | Feng X, Mueller T, Mizrachi D, Fanelli F, Segaloff DL An intracellular loop (IL2) residue confers different basal constitutive activities to the human lutropin receptor and human thyrotropin receptor through structural communication between IL2 and helix 6, via helix 3 Endocrinology. 2008 Apr;149(4):1705-17 Pubmed | Ulloa-Aguirre A, Uribe A, Zariñán T, Bustos-Jaimes I, Pérez-Solis MA, Dias JA Role of the intracellular domains of the human FSH receptor in G(alphaS) protein coupling and receptor expression. Mol Cell Endocrinol. 2007 Jan 2;260-262:153-62 Pubmed | Claus M, Neumann S, Kleinau G, Krause G, Paschke R. Structural determinants for G-protein activation and specificity in the third intracellular loop of the thyroid-stimulating hormone receptor. J Mol Med. 2006 Nov;84(11):943-54 Pubmed | Timossi C, Ortiz-Elizondo C, Pineda DB, Dias JA, Conn PM, Ulloa-Aguirre A Functional significance of the BBXXB motif reversed present in the cytoplasmic domains of the human follicle-stimulating hormone receptor Mol Cell Endocrinol. 2004 Aug 31;223(1-2):17-26 Pubmed | Bhaskaran RS, Min L, Krishnamurthy H, Ascoli M. Studies with chimeras of the gonadotropin receptors reveal the importance of third intracellular loop threonines on the formation of the receptor/nonvisual arrestin complex. Biochemistry. 2003 Dec 2;42(47):13950-9 Pubmed | Schulz A, Bruns K, Henklein P, Krause G, Schubert M, Gudermann T, Wray V, Schultz G, Schoneberg T Requirement of specific intrahelical interactions for stabilizing the inactive conformation of glycoprotein hormone receptors J Biol Chem. 2000 Dec 1;275(48):37860-9 Pubmed | Schulz A, Schoneberg T, Paschke R, Schultz G, Gudermann T Role of the third intracellular loop for the activation of gonadotropin receptors Mol Endocrinol. 1999 Feb;13(2):181-90 Pubmed | Wang H, Jaquette J, Collison K, Segaloff DL Positive charges in a putative amphiphilic helix in the carboxyl-terminal region of the third intracellular loop of the luteinizing hormone/chorionic gonadotropin receptor are not required for hormone-stimulated cAMP production but are necessary for expression of the receptor at the plasma membrane Mol Endocrinol. 1993 Nov;7(11):1437-44 Pubmed | Kosugi S, Okajima F, Ban T, Hidaka A, Shenker A, Kohn LD Substitutions of different regions of the third cytoplasmic loop of the thyrotropin (TSH) receptor have selective effects on constitutive, TSH-, and TSH receptor autoantibody-stimulated phosphoinositide and 3',5'-cyclic adenosine monophosphate signal generation. Mol Endocrinol. 1993 Aug;7(8):1009-20 Pubmed | Chazenbalk GD, Nagayama Y, Wadsworth H, Russo D, Rapoport B. Signal transduction by the human thyrotropin receptor: studies on the role of individual amino acid residues in the carboxyl terminal region of the third cytoplasmic loop. Mol Endocrinol. 1991 Oct;5(10):1523-6 Pubmed | Chazenbalk GD, Nagayama Y, Russo D, Wadsworth HL, Rapoport B Functional analysis of the cytoplasmic domains of the human thyrotropin receptor by site-directed mutagenesis J Biol Chem. 1990 Dec 5;265(34):20970-5 Pubmed | |
Ionic influence
Munshi UM, Pogozheva ID, Menon KM Highly conserved serine in the third transmembrane helix of the luteinizing hormone/human chorionic gonadotropin receptor regulates receptor activation Biochemistry. 2003 Apr 8;42(13):3708-15 Pubmed | Angelova K, Puett D Differential responses of an invariant region in the ectodomain of three glycoprotein hormone receptors to mutagenesis and assay conditions Endocrine. 2002 Nov;19(2):147-54 Pubmed | Cetani F, Tonacchera M, Vassart G Differential effects of NaCl concentration on the constitutive activity of the thyrotropin and the luteinizing hormone/chorionic gonadotropin receptors FEBS Lett. 1996 Jan 2;378(1):27-31 Pubmed | Quintana J, Wang H, Ascoli M The regulation of the binding affinity of the luteinizing hormone/choriogonadotropin receptor by sodium ions is mediated by a highly conserved aspartate located in the second transmembrane domain of G protein-coupled receptors Mol Endocrinol. 1993 Jun;7(6):767-75 Pubmed | |
Dimerization
Guan R, Wu X, Feng X, Zhang M, Hebert TE, Segaloff DL Structural determinants underlying constitutive dimerization of unoccupied human follitropin receptors Cell Signal. 2010 Feb;22(2):247-56 Pubmed | Rivero-Müller A, Chou YY, Ji I, Lajic S, Hanyaloglu AC, Jonas K, Rahman N, Ji TH, Huhtaniemi I Rescue of defective G protein-coupled receptor function in vivo by intermolecular cooperation. Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2319-24 Pubmed | Zhang M, Feng X, Guan R, Hébert TE, Segaloff DL. A cell surface inactive mutant of the human lutropin receptor (hLHR) attenuates signaling of wild-type or constitutively active receptors via heterodimerization. Cell Signal. 2009 Nov;21(11):1663-71. Pubmed | Guan R, Feng X, Wu X, Zhang M, Zhang X, Hébert TE, Segaloff DL Bioluminescence resonance energy transfer studies reveal constitutive dimerization of the human lutropin receptor and a lack of correlation between receptor activation and the propensity for dimerization J Biol Chem. 2009 Mar 20;284(12):7483-94. Epub 2009 Jan 15 Pubmed | Svendsen AM, Vrecl M, Knudsen L, Heding A, Wade JD, Bathgate RA, De Meyts P, Nøhr J. Dimerization and negative cooperativity in the relaxin family peptide receptors. Ann N Y Acad Sci. 2009 Apr;1160:54-9 Pubmed | Svendsen AM, Vrecl M, Ellis TM, Heding A, Kristensen JB, Wade JD, Bathgate RA, De Meyts P, Nøhr J. Cooperative binding of insulin-like Peptide 3 to a dimeric relaxin family peptide receptor 2. Endocrinology. 2008 Mar;149(3):1113-20 Pubmed | Fanelli F. Dimerization of the lutropin receptor: Insights from computational modeling. Mol Cell Endocrinol. 2007 Jan 2;260-262:59-64 Pubmed | Persani L, Calebiro D, Bonomi M. Technology Insight: modern methods to monitor protein-protein interactions reveal functional TSH receptor oligomerization. Nat Clin Pract Endocrinol Metab. 2007 Feb;3(2):180-90 Pubmed | Urizar E, Montanelli L, Loy T, Bonomi M, Swillens S, Gales C, Bouvier M, Smits G, Vassart G, Costagliola S Glycoprotein hormone receptors: link between receptor homodimerization and negative cooperativity EMBO J.2005 Jun 1;24(11):1954-64 Pubmed | Calebiro D, de Filippis T, Lucchi S, Covino C, Panigone S, Beck-Peccoz P, Dunlap D, Persani L. Intracellular entrapment of wild-type TSH receptor by oligomerization with mutants linked to dominant TSH resistance. Hum Mol Genet. 2005 Oct 15;14(20):2991-3002 Pubmed | Tao YX, Johnson NB, Segaloff DL Constitutive and agonist-dependent self-association of the cell surface human lutropin receptor J Biol Chem. 2004 Feb 13;279(7):5904-14 Pubmed | Ji I, Lee C, Jeoung M, Koo Y, Sievert GA, Ji TH Trans-activation of mutant follicle-stimulating hormone receptors selectively generates only one of two hormone signals Mol Endocrinol. 2004 Apr;18(4):968-78 Pubmed | Latif R, Graves P, Davies TF Ligand-dependent inhibition of oligomerization at the human thyrotropin receptor J Biol Chem. 2002 Nov 22;277(47):45059-67 Pubmed | Ji I, Lee C, Song Y, Conn PM, Ji TH Cis- and trans-activation of hormone receptors: the LH receptor Mol Endocrinol. 2002 Jun;16(6):1299-308 Pubmed | Davies T, Marians R, Latif R The TSH receptor reveals itself J Clin Invest. 2002 Jul;110(2):161-4 Pubmed | Latif R, Graves P, Davies TF Oligomerization of the human thyrotropin receptor: fluorescent protein-tagged hTSHR reveals post-translational complexes J Biol Chem. 2001 Nov 30;276(48):45217-24 Pubmed | Osuga Y, Hayashi M, Kudo M, Conti M, Kobilka B, Hsueh AJ Co-expression of defective luteinizing hormone receptor fragments partially reconstitutes ligand-induced signal generation J Biol Chem. 1997 Oct 3;272(40):25006-12 Pubmed | Osuga Y, Kudo M, Kaipia A, Kobilka B, Hsueh AJ Derivation of functional antagonists using N-terminal extracellular domain of gonadotropin and thyrotropin receptors Mol Endocrinol. 1997 Oct;11(11):1659-68 Pubmed | Graves PN, Vlase H, Bobovnikova Y, Davies TF Multimeric complex formation by the thyrotropin receptor in solubilized thyroid membranes Endocrinology. 1996 Sep;137(9):3915-20 Pubmed | Graves PN, Vlase H, Davies TF Folding of the recombinant human thyrotropin (TSH) receptor extracellular domain: identification of folded monomeric and tetrameric complexes that bind TSH receptor autoantibodies Endocrinology. 1995 Feb;136(2):521-7 Pubmed | Dattatreyamurty B, Smith RA, Zhang SB, Santa-Coloma TA, Reichert LE Jr The size of the mature membrane receptor for follicle-stimulating hormone is larger than that predicted from its cDNA J Mol Endocrinol. 1992 Oct;9(2):115-21 Pubmed | |
Molecular Models
Mueller S, Kleinau G, Jaeschke H, Paschke R, Krause G. Extended Hormone Binding Site of the Human Thyroid Stimulating Hormone Receptor: DISTINCTIVE ACIDIC RESIDUES IN THE HINGE REGION ARE INVOLVED IN BOVINE THYROID STIMULATING HORMONE BINDING AND RECEPTOR ACTIVATION. J Biol Chem. 2008 Jun 27;283(26):18048-55 Pubmed | Fanelli F. Dimerization of the lutropin receptor: Insights from computational modeling. Mol Cell Endocrinol. 2007 Jan 2;260-262:59-64 Pubmed | Puett D, Li Y, Demars G, Angelova K, Fanelli F. A functional transmembrane complex: The luteinizing hormone receptor with bound ligand and G protein Mol Cell Endocrinol. 2007 Jan 2;260-262:126-36. Pubmed | Kleinau G, Claus M, Jaeschke H, Mueller S, Neumann S, Paschke R, Krause G. Contacts between extracellular loop two and transmembrane helix six determine basal activity of the thyroid stimulating hormone receptor. J Biol Chem. 2007 Jan 5;282(1):518-25 Pubmed | Jaeschke H, Neumann S, Kleinau G, Mueller S, Claus M, Krause G, Paschke R An aromatic environment in the vicinity of serine281 is a structural requirement for TSH receptor function Endocrinology. 2006 Apr;147(4):1753-60 Pubmed | Mueller S, Kleinau G, Jaeschke H, Neumann S, Krause G, Paschke R. Significance of ectodomain cysteine boxes 2 and 3 for the activation mechanism of the thyroid-stimulating hormone receptor. J Biol Chem. 2006 Oct 20;281(42):31638-46. Pubmed | Claus M, Neumann S, Kleinau G, Krause G, Paschke R. Structural determinants for G-protein activation and specificity in the third intracellular loop of the thyroid-stimulating hormone receptor. J Mol Med. 2006 Nov;84(11):943-54 Pubmed | Urizar E, Claeysen S, Deupi X, Govaerts C, Costagliola S, Vassart G, Pardo L An Activation Switch in the Rhodopsin Family of G Protein-coupled Receptors: THE THYROTROPIN RECEPTOR J Biol Chem. 2005 Apr 29;280(17):17135-41 Pubmed | Zhang M, Mizrachi D, Fanelli F, Segaloff DL The formation of a salt bridge between helices 3 and 6 is responsible for the constitutive activity and lack of hormone responsiveness of the naturally occurring L457R mutation of the human lutropin receptor. J Biol Chem. 2005 Jul 15;280(28):26169-76 Pubmed | Karges B, Krause G, Homoki J, Debatin KM, de Roux N, Karges W. TSH receptor mutation V509A causes familial hyperthyroidism by release of interhelical constraints between transmembrane helices TMH3 and TMH5. J Endocrinol. 2005 Aug;186(2):377-85 Pubmed | Claus M, Jaeschke H, Kleinau G, Neumann S, Krause G, Paschke R A hydrophobic cluster in the center of the third extracellular loop is important for thyrotropin receptor signaling Endocrinology. 2005 Dec;146(12):5197-203 Pubmed | Fanelli F, Verhoef-Post M, Timmerman M, Zeilemaker A, Martens JW, Themmen AP Insight into mutation-induced activation of the luteinizing hormone receptor: molecular simulations predict the functional behavior of engineered mutants at M398 Mol Endocrinol. 2004 Jun;18(6):1499-508 Pubmed | Montanelli L, Van Durme JJ, Smits G, Bonomi M, Rodien P, Devor EJ, Moffat-Wilson K, Pardo L, Vassart G, Costagliola S. Modulation of ligand selectivity associated with activation of the transmembrane region of the human follitropin receptor. Mol Endocrinol. 2004 Aug;18(8):2061-73 Pubmed | Moyle WR, Xing Y, Lin W, Cao D, Myers RV, Kerrigan JE, Bernard MP Model of glycoprotein hormone receptor ligand binding and signaling J Biol Chem. 2004 Oct 22;279(43):44442-59 Pubmed | Nunez Miguel R, Sanders J, Jeffreys J, Depraetere H, Evans M, Richards T, Blundell TL, Rees Smith B, Furmaniak J Analysis of the thyrotropin receptor-thyrotropin interaction by comparative modeling Thyroid. 2004 Dec;14(12):991-1011 Pubmed | Kleinau G, Jaschke H, Neumann S, Lattig J, Paschke R, Krause G Identification of a novel epitope in the thyroid-stimulating hormone receptor ectodomain acting as intramolecular signaling interface J Biol Chem. 2004 Dec 3;279(49):51590-600 Pubmed | Munshi UM, Pogozheva ID, Menon KM Highly conserved serine in the third transmembrane helix of the luteinizing hormone/human chorionic gonadotropin receptor regulates receptor activation. Biochemistry. 2003 Apr 8;42(13):3708-15 Pubmed | Fanelli F, Puett D Structural aspects of luteinizing hormone receptor: information from molecular modeling and mutagenesis Endocrine. 2002 Aug;18(3):285-93 Pubmed | Angelova K, Fanelli F, Puett D A model for constitutive lutropin receptor activation based on molecular simulation and engineered mutations in transmembrane helices 6 and 7 J Biol Chem. 2002 Aug 30;277(35):32202-13 Pubmed | Neumann S, Krause G, Chey S, Paschke R A free carboxylate oxygen in the side chain of position 674 in transmembrane domain 7 is necessary for TSH receptor activation Mol Endocrinol. 2001 Aug;15(8):1294-305 Pubmed | Fanelli F Theoretical study on mutation-induced activation of the luteinizing hormone receptor J Mol Biol. 2000 Mar 10;296(5):1333-51 Pubmed | Schulz A, Bruns K, Henklein P, Krause G, Schubert M, Gudermann T, Wray V, Schultz G, Schoneberg T Requirement of specific intrahelical interactions for stabilizing the inactive conformation of glycoprotein hormone receptors J Biol Chem. 2000 Dec 1;275(48):37860-9 Pubmed | Lin Z, Shenker A, Pearlstein R A model of the lutropin/choriogonadotropin receptor: insights into the structural and functional effects of constitutively activating mutations Protein Eng. 1997 May;10(5):501-10 Pubmed | |
Small Molecules
Haas AK, Kleinau G, Hoyer I, Neumann S, Furkert J, Rutz C, Schülein R, Gershengorn MC, Krause G. Mutations that silence constitutive signaling activity in the allosteric ligand-binding site of the thyrotropin receptor. Cell Mol Life Sci. 2011 Jan;68(1):159-67 Pubmed | Kleinau G, Haas AK, Neumann S, Worth CL, Hoyer I, Furkert J, Rutz C, Gershengorn MC, Schülein R, Krause G. Signaling-sensitive amino acids surround the allosteric ligand binding site of the thyrotropin receptor. FASEB J. 2010 Jul;24(7):2347-54 Pubmed | Dias JA, Bonnet B, Weaver BA, Watts J, Kluetzman K, Thomas RM, Poli SM, Mutel V, Campo B. A negative allosteric modulator demonstrates biased antagonism of the follicle stimulating hormone receptor. Mol Cell Endocrinol. 2010 Dec 22. [Epub ahead of print] Pubmed | Neumann S, Huang W, Titus S, Krause G, Kleinau G, Alberobello AT, Zheng W, Southall NT, Inglese J, Austin CP, Celi FS, Gavrilova O, Thomas CJ, Raaka BM, Gershengorn MC Small-molecule agonists for the thyrotropin receptor stimulate thyroid function in human thyrocytes and mice. Proc Natl Acad Sci U S A. 2009 Jul 28;106(30):12471-6. Pubmed | Heitman LH, Narlawar R, de Vries H, Willemsen MN, Wolfram D, Brussee J, Ijzerman AP. Substituted terphenyl compounds as the first class of low molecular weight allosteric inhibitors of the luteinizing hormone receptor. J Med Chem. 2009 Apr 9;52(7):2036-42. Pubmed | Bonger KM, van den Berg RJ, Knijnenburg AD, Heitman LH, van Koppen CJ, Timmers CM, Overkleeft HS, van der Marel GA. Discovery of selective luteinizing hormone receptor agonists using the bivalent ligand method. ChemMedChem. 2009 Jul;4(7):1189-95. Pubmed | Neumann S, Raaka BM, Gershengorn MC. Human TSH receptor ligands as pharmacological probes with potential clinical application. Expert Rev Endocrinol Metab. 2009 Nov 1;4(6):669 Pubmed | Haugen BR. Drugs that suppress TSH or cause central hypothyroidism. Best Pract Res Clin Endocrinol Metab. 2009 Dec;23(6):793-800 Pubmed | Arey BJ, Yanofsky SD, Claudia Pérez M, Holmes CP, Wrobel J, Gopalsamy A, Stevis PE, López FJ, Winneker RC. Differing pharmacological activities of thiazolidinone analogs at the FSH receptor Biochem Biophys Res Commun. 2008 Apr 11;368(3):723-8 Pubmed | Heitman L, Oosterom J, Bonger K, Timmers C, Wiegerinck P, Ijzerman AP [3H]Org 43553, the First Low Molecular Weight Agonistic and Allosteric Radioligand for the Human Luteinizing Hormone Receptor Mol Pharmacol. 2008 Feb;73(2):518-24 Pubmed | van Koppen CJ, Zaman GJ, Timmers CM, Kelder J, Mosselman S, van de Lagemaat R, Smit MJ, Hanssen RG A signaling-selective, nanomolar potent allosteric low molecular weight agonist for the human luteinizing hormone receptor Naunyn Schmiedebergs Arch Pharmacol. 2008 Nov;378(5):503-14 Pubmed | Heitman LH, Ijzerman AP G protein-coupled receptors of the hypothalamic-pituitary-gonadal axis: a case for Gnrh, LH, FSH, and GPR54 receptor ligands Med Res Rev. 2008 Nov;28(6):975-1011 Pubmed | Neumann S, Kleinau G, Costanzi S, Moore S, Jiang JK, Raaka BM, Thomas CJ, Krause G, Gershengorn MC. A low-molecular-weight antagonist for the human thyrotropin receptor with therapeutic potential for hyperthyroidism. Endocrinology. 2008 Dec;149(12):5945-50 Pubmed | Arey BJ. Allosteric modulators of glycoprotein hormone receptors: discovery and therapeutic potential. Endocrine. 2008 Aug-Dec;34(1-3):1-10. Epub 2008 Oct 28. Pubmed | Jorand-Lebrun C, Brondyk B, Lin J, Magar S, Murray R, Reddy A, Shroff H, Wands G, Weiser W, Xu Q, McKenna S, Brugger N Identification, synthesis, and biological evaluation of novel pyrazoles as low molecular weight luteinizing hormone receptor agonists Bioorg Med Chem Lett. 2007 Apr 1;17(7):2080-5 Pubmed | Jaschke H, Neumann S, Moore S, Thomas CJ, Colson AO, Costanzi S, Kleinau G, Jiang JK, Paschke R, Raaka BM, Krause G, Gershengorn MC A low molecular weight agonist signals by binding to the transmembrane domain of thyroid-stimulating hormone receptor (TSHR) and luteinizing hormone/chorionic gonadotropin receptor (LHCGR) J Biol Chem. 2006 Apr 14;281(15):9841-4 Pubmed | Yanofsky SD, Shen ES, Holden F, Whitehorn E, Aguilar B, Tate E, Holmes CP, Scheuerman R, MacLean D, Wu MM, Frail DE, Lopez FJ, Winneker R, Arey BJ, Barrett RW Allosteric activation of the follicle-stimulating hormone (FSH) receptor by selective, nonpeptide agonists J Biol Chem. 2006 May 12;281(19):13226-33 Pubmed | Wrobel J, Jetter J, Kao W, Rogers J, Di L, Chi J, Perez MC, Chen GC, Shen ES 5-Alkylated thiazolidinones as follicle-stimulating hormone (FSH) receptor agonists Bioorg Med Chem. 2006 Aug 15;14(16):5729-41 Pubmed | van Straten NC, van Berkel TH, Demont DR, Karstens WJ, Merkx R, Oosterom J, Schulz J, van Someren RG, Timmers CM, van Zandvoort PM Identification of substituted 6-amino-4-phenyltetrahydroquinoline derivatives: potent antagonists for the follicle-stimulating hormone receptor J Med Chem. 2005 Mar 24;48(6):1697-700 Pubmed | Pelletier JC, Rogers J, Wrobel J, Perez MC, Shen ES Preparation of highly substituted gamma-lactam follicle stimulating hormone receptor agonists Bioorg Med Chem. 2005 Nov 1;13(21):5986-95 Pubmed | Wrobel J, Green D, Jetter J, Kao W, Rogers J, Perez MC, Hardenburg J, Deecher DC, Lopez FJ, Arey BJ, Shen ES Synthesis of (bis)sulfonic acid, (bis)benzamides as follicle-stimulating hormone (FSH) antagonists Bioorg Med Chem. 2002 Mar;10(3):639-569 Pubmed | Arey BJ, Deecher DC, Shen ES, Stevis PE, Meade EH Jr, Wrobel J, Frail DE, Lopez FJ Identification and characterization of a selective, nonpeptide follicle-stimulating hormone receptor antagonist Endocrinology. 2002 Oct;143(10):3822-9 Pubmed | |
LGRs4-8
Barker N, Clevers H Leucine-rich repeat-containing G-protein-coupled receptors as markers of adult stem cells. Gastroenterology. 2010 May;138(5):1681-96. Pubmed | Snippert HJ, Haegebarth A, Kasper M, Jaks V, van Es JH, Barker N, van de Wetering M, van den Born M, Begthel H, Vries RG, Stange DE, Toftg�rd R, Clevers H. Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science. 2010 Mar 12;327(5971):1385-9. Pubmed | Svendsen AM, Vrecl M, Knudsen L, Heding A, Wade JD, Bathgate RA, De Meyts P, Nøhr J. Dimerization and negative cooperativity in the relaxin family peptide receptors. Ann N Y Acad Sci. 2009 Apr;1160:54-9 Pubmed | Yan Y, Scott DJ, Wilkinson TN, Ji J, Tregear GW, Bathgate RA Identification of the N-linked glycosylation sites of the human relaxin receptor and effect of glycosylation on receptor function. Biochemistry. 2008 Jul 1;47(26):6953-68 Pubmed | Svendsen AM, Vrecl M, Ellis TM, Heding A, Kristensen JB, Wade JD, Bathgate RA, De Meyts P, Nøhr J. Cooperative binding of insulin-like Peptide 3 to a dimeric relaxin family peptide receptor 2. Endocrinology. 2008 Mar;149(3):1113-20 Pubmed | Morgan BA. A glorious revolution in stem cell biology. Nat Genet. 2008 Nov;40(11):1269-70 Pubmed | Krusche CA, Kroll T, Beier HM, Classen-Linke I Expression of leucine-rich repeat-containing G-protein-coupled receptors in the human cyclic endometrium Fertil Steril. 2007 Jun;87(6):1428-37 Pubmed | Hoshii T, Takeo T, Nakagata N, Takeya M, Araki K, Yamamura K LGR4 Regulates the Postnatal Development and Integrity of Male Reproductive Tracts in Mice Biol Reprod. 2007 Feb;76(2):303-13 Pubmed | Van Loy T, Vandersmissen HP, Van Hiel MB, Poels J, Verlinden H, Badisco L, Vassart G, Vanden Broeck J Comparative genomics of leucine-rich repeats containing G protein-coupled receptors and their ligands Gen Comp Endocrinol. 2007 Jul 4 Pubmed | Scott DJ, Wilkinson TN, Zhang S, Ferraro T, Wade JD, Tregear GW, Bathgate RA Defining the LGR8 residues involved in binding insulin-like peptide 3 Mol Endocrinol. 2007 Jul;21(7):1699-712 Pubmed | Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007 Oct 25;449(7165):1003-7 Pubmed | Luo CW, Hsueh AJ Genomic analyses of the evolution of LGR genes Chang Gung Med J. 2006 Jan-Feb;29(1):2-8. Review Pubmed | Kato S, Matsubara M, Matsuo T, Mohri Y, Kazama I, Hatano R, Umezawa A, Nishimori K Leucine-rich repeat-containing G protein-coupled receptor-4 (LGR4, Gpr48) is essential for renal development in mice Nephron Exp Nephrol. 2006;104(2):e63-75 Pubmed | Bathgate RA, Lin F, Hanson NF, Otvos L Jr, Guidolin A, Giannakis C, Bastiras S, Layfield SL, Ferraro T, Ma S, Zhao C, Gundlach AL, Samuel CS, Tregear GW, Wade JD Relaxin-3: improved synthesis strategy and demonstration of its high-affinity interaction with the relaxin receptor LGR7 both in vitro and in vivo Biochemistry. 2006 Jan 24;45(3):1043-53 Pubmed | Scott DJ, Layfield S, Yan Y, Sudo S, Hsueh AJ, Tregear GW, Bathgate RA Characterization of novel splice variants of LGR7 and LGR8 reveals that receptor signaling is mediated by their unique low density lipoprotein class A modules. J Biol Chem. 2006 Nov 17;281(46):34942-54 Pubmed | Liu C, Chen J, Kuei C, Sutton S, Nepomuceno D, Bonaventure P, Lovenberg TW Relaxin-3/insulin-like peptide 5 chimeric peptide, a selective ligand for G protein-coupled receptor (GPCR)135 and GPCR142 over leucine-rich repeat-containing G protein-coupled receptor 7. Mol Pharmacol. 2005 Jan;67(1):231-40 Pubmed | Scott DJ, Tregear GW, Bathgate RA LGR7-truncate is a splice variant of the relaxin receptor LGR7 and is a relaxin antagonist in vitro Ann N Y Acad Sci. 2005 May;1041:22-6 Pubmed | Hsu SY, Semyonov J, Park JI, Chang CL Evolution of the signaling system in relaxin-family peptides Ann N Y Acad Sci. 2005 May;1041:520-9 Pubmed | Van Schoore G, Mendive F, Pochet R, Vassart G Expression pattern of the orphan receptor LGR4/GPR48 gene in the mouse Histochem Cell Biol. 2005 Jul;124(1):35-50 Pubmed | Park JI, Semyonov J, Chang CL, Hsu SY Conservation of the heterodimeric glycoprotein hormone subunit family proteins and the LGR signaling system from nematodes to humans Endocrine. 2005 Apr;26(3):267-76 Pubmed | Muda M, He C, Martini PG, Ferraro T, Layfield S, Taylor D, Chevrier C, Schweickhardt R, Kelton C, Ryan PL, Bathgate RA Splice variants of the relaxin and INSL3 receptors reveal unanticipated molecular complexity Mol Hum Reprod. 2005 Aug;11(8):591-600 Pubmed | Fu P, Shen PJ, Zhao CX, Scott DJ, Samuel CS, Wade JD, Tregear GW, Bathgate RA, Gundlach AL Detection, localization, and action of the INSL3 receptor, LGR8, in rat kidney Ann N Y Acad Sci. 2005 May;1041:516-9 Pubmed | Lin F, Otvos L Jr, Kumagai J, Tregear GW, Bathgate RA, Wade JD Synthetic human insulin 4 does not activate the G-protein-coupled receptors LGR7 or LGR8 J Pept Sci. 2004 May;10(5):257-64 Pubmed | Mazerbourg S, Bouley DM, Sudo S, Klein CA, Zhang JV, Kawamura K, Goodrich LV, Rayburn H, Tessier-Lavigne M, Hsueh AJ Leucine-rich repeat-containing, G protein-coupled receptor 4 null mice exhibit intrauterine growth retardation associated with embryonic and perinatal lethality. Mol Endocrinol. 2004 Sep;18(9):2241-54 Pubmed | Morita H, Mazerbourg S, Bouley DM, Luo CW, Kawamura K, Kuwabara Y, Baribault H, Tian H, Hsueh AJ Neonatal lethality of LGR5 null mice is associated with ankyloglossia and gastrointestinal distension Mol Cell Biol. 2004 Nov;24(22):9736-43 Pubmed | Herpin A, Badariotti F, Rodet F, Favrel P Molecular characterization of a new leucine-rich repeat-containing G protein-coupled receptor from a bivalve mollusc: evolutionary implications Biochim Biophys Acta. 2004 Nov 5;1680(3):137-44 Pubmed | Hsu SY New insights into the evolution of the relaxin-LGR signaling system Trends Endocrinol Metab. 2003 Sep;14(7):303-9. Review Pubmed | Hsu SY, Nakabayashi K, Nishi S, Kumagai J, Kudo M, Sherwood OD, Hsueh AJ Activation of orphan receptors by the hormone relaxin Science. 2002 Jan 25;295(5555):671-4 Pubmed | Kudo M, Chen T, Nakabayashi K, Hsu SY, Hsueh AJ The nematode leucine-rich repeat-containing, G protein-coupled receptor (LGR) protein homologous to vertebrate gonadotropin and thyrotropin receptors is constitutively active in mammalian cells Mol Endocrinol. 2000 Feb;14(2):272-84 Pubmed | Eriksen KK, Hauser F, Schiott M, Pedersen KM, Sondergaard L, Grimmelikhuijzen CJ Molecular cloning, genomic organization, developmental regulation, and a knock-out mutant of a novel leu-rich repeats-containing G protein-coupled receptor (DLGR-2) from Drosophila melanogaster. Genome Res. 2000 Jul;10(7):924-38 Pubmed | Hsu SY, Kudo M, Chen T, Nakabayashi K, Bhalla A, van der Spek PJ, van Duin M, Hsueh AJ The three subfamilies of leucine-rich repeat-containing G protein-coupled receptors (LGR): identification of LGR6 and LGR7 and the signaling mechanism for LGR7. Mol Endocrinol. 2000 Aug;14(8):1257-71 Pubmed | Nishi S, Hsu SY, Zell K, Hsueh AJ Characterization of two fly LGR (leucine-rich repeat-containing, G protein-coupled receptor) proteins homologous to vertebrate glycoprotein hormone receptors: constitutive activation of wild-type fly LGR1 but not LGR2 in transfected mammalian cells. Endocrinology. 2000 Nov;141(11):4081-90 Pubmed | Hsu SY, Liang SG, Hsueh AJ. Characterization of two LGR genes homologous to gonadotropin and thyrotropin receptors with extracellular leucine-rich repeats and a G protein-coupled, seven-transmembrane region. Mol Endocrinol. 1998 Dec;12(12):1830-45. Pubmed | |