Activating mutations of the lutropin choriogonadotropin receptor in precocious puberty

Receptors and Channels

Volumn 8, Issue 1, 2002, Pages 3-18

  Shenker, Andrew ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

Author keywords

Constitutive activity; G protein coupled receptor; Leydig cell; LH receptor; Mutation; Precocious puberty

Indexed keywords

ADENYLATE CYCLASE; CHORIONIC GONADOTROPIN RECEPTOR; CYPROTERONE; FOLLITROPIN; G PROTEIN COUPLED RECEPTOR; GLYCOPROTEIN; GONADORELIN DERIVATIVE; KETOCONAZOLE; LUTEINIZING HORMONE; LUTEINIZING HORMONE RECEPTOR; RHODOPSIN; SPIRONOLACTONE; TESTOLACTONE; TESTOSTERONE; THYROTROPIN;

ANIMAL CELL; CATTLE; CELL GROWTH; CELL HYPERPLASIA; CELL MEMBRANE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DNA HELIX; ELECTRICITY; GENE MUTATION; GENETIC HETEROGENEITY; HUMAN; HYDROGEN BOND; HYDROPHOBICITY; LEYDIG CELL; LEYDIG CELL TUMOR; MALE; NONHUMAN; PHENOTYPE; PRECOCIOUS PUBERTY; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN FUNCTION; PROTEIN MOTIF; PROTEIN STRUCTURE; REPRODUCTION; REVIEW; SIGNAL TRANSDUCTION; SOMATIC MUTATION; STRUCTURE ANALYSIS; AMINO ACID SEQUENCE; CELL DIVISION; CHEMICAL STRUCTURE; CHEMISTRY; GENETICS; MOLECULAR GENETICS; MUTATION; PATHOLOGY; PATHOPHYSIOLOGY; SECOND MESSENGER;

AMINO ACID SEQUENCE; CELL DIVISION; HUMAN; LEYDIG CELLS; MALE; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTATION; PUBERTY, PRECOCIOUS; RECEPTORS, LH; SECOND MESSENGER SYSTEMS; SUPPORT, NON-U.S. GOV'T; SUPPORT, U.S. GOV'T, P.H.S.; HUMANS;

ANIMALIA; BOS TAURUS; BOVINAE;

EID: 0035989009     PISSN: 10606823     EISSN: None     Source Type: Journal    
DOI: 10.1080/10606820212138     Document Type: Review

References (179)

1. Light-induced exposure of the cytoplasmic end of transmembrane helix seven in rhodopsin
2. Certain activating mutations within helix 6 of the human luteinizing hormone receptor may be explained by alterations that allow transmembrane regions to activate Gs
3. Luteinizing hormone (LH) drives diverse intracellular calcium second messenger signals in isolated porcine ovarian thecal cells: Preferential recruitment of intracellular Ca2+ oscillatory cells by higher concentrations of LH
4. A novel germline mutation in the TSH receptor gene causes non-autoimmune autosomal dominant hyperthyroidism
5. Structural features and light-dependent changes in the sequence 306-322 extending from helix VII to the palmitoylation sites in rhodopsin: A site-directed spin-labeling study
6. Functional role of transmembrane helix 7 in the activation of the heptahelical lutropin receptor
7. The role of interactions between transmembrane helices 6 and 7 in constitutive activation of the LH receptor
8. Role of gonadotrophins in regulating numbers of Leydig and Sertoli cells during fetal and postnatal development in mice
9. An alpha-carbon template for the transmembrane helices in the rhodopsin family of G-protein-coupled receptors
10. Serine and threonine residues bend alpha-helices in the chi(1) = g(-) conformation
11. Activation of the beta 2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6
12. Structural mimicry in G protein-coupled receptors: Implications of the high-resolution structure of rhodopsin for structure-function analysis of rhodopsin-like receptors
13. Functional microdomains in G-protein-coupled receptors. The conserved arginine-cage motif in the gonadotropin-releasing hormone receptor
14. C5a receptor activation. Genetic identification of critical residues in four transmembrane helices
15. Adenovirus-directed expression of functional luteinizing hormone (LH) receptors in undifferentiated rat granulosa cells: Evidence for differential signaling through follicle-stimulating hormone and LH receptors
16. Constitutive activation of the delta opioid receptor by mutations in transmembrane domains III and VII
17. Determination of residues important in hormone binding to the extracellular domain of the luteinizing hormone/chorionic gonadotropin receptor by site-directed mutagenesis and modeling
18. A conserved tyrosine residue (Y601) in transmembrane domain 5 of the human thyrotropin receptor serves as a molecular switch to determine G-protein coupling
19. G-protein coupled receptors: Models, mutagenesis, and drug design
20. Post-translational processing in the Golgi plays a critical role in the trafficking of the luteinizing hormone/human chorionic gonadotropin receptor to the cell surface
21. Differential effects of NaCl concentration on the constitutive activity of the thyrotropin and luteinizing hormone/chorionic gonadotropin receptors
22. Constitutive activation of A(3) adenosine receptors by site-directed mutagenesis
23. Dominant-negative activity of an alpha(1B)-adrenergic receptor signal-inactivating point mutation
24. Novel brain-specific 5-HT4 receptor splice variants show marked constitutive activity: Role of the C-terminal intracellular domain
25. A missense (T577I) mutation in the luteinizing hormone receptor gene associated with familial male-limited precocious puberty
26. Characterization of gonadal pathology in males with McCune-Albright syndrome
27. Somatic and germline mutations of the TSH receptor and thyroid diseases
28. A requirement for cyclin D3-cyclin-dependent kinase (cdk)-4 assembly in the cyclic adenosine monophosphate-dependent proliferation of thyrocytes
29. The luteinizing hormone receptor
30. Creation of a constitutively activated state of the 5-hydroxytryptamine2A receptor by site-directed mutagenesis: Inverse agonist activity of antipsychotic drugs
31. Conversion of agonist site to metal-ion chelator site in the beta(2)-adrenergic receptor
32. 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
33. A new point mutation in the luteinising hormone receptor gene in familial and sporadic male limited precocious puberty: Genotype does not always correlate with phenotype
34. Theoretical study on mutation-induced activation of the luteinizing hormone receptor
35. Light activation of rhodopsin requires rigid body motion of transmembrane helices
36. 583 in the third extracellular loop of the lutropin/choriogonadotropin receptor is critical for signaling
37. An activation switch in the ligand binding pocket of the C5a receptor
38. Minireview: Insights into G protein-coupled receptor function using molecular models
39. Uncovering molecular mechanisms involved in activation of G protein-coupled receptors
40. 2 adrenoceptor
41. The luteinizing hormone/chorionic gonadotropin receptor has distinct transmembrane conductors for cAMP and inositol phosphate signals
42. The TxP motif in the second transmembrane helix of CCR5: A structural determinant of chemokine-induced activation
43. A conserved Asn in transmembrane helix 7 is an on/off switch in the activation of the thyrotropin receptor
44. Intrahelical hydrogen bonding of serine, threonine and cysteine residues within α-helices and its relevance to membrane-bound proteins
45. Mutational and computational analysis of the alpha1b-adrenergic receptor: Involvement of basic and hydrophobic residues in receptor activation and G protein coupling
46. A mutation in the first transmembrane domain of the lutropin receptor causes male precocious puberty
47. Origin, differentiation and regulation of fetal and adult Leydig cells
48. Functional helix-helix interactions in rhodopsin: Replacement of phenylalanine 261 by alanine causes reversion of phenotype of a glycine 121 replacement mutant
49. Constitutive activation of opsin by mutation of methionine 257 on transmembrane helix 6
50. Molecular cloning, genomic organization, and developmental regulation of a novel receptor from Drosophila melanogaster structurally related to members of the thyroid-stimulating hormone, follicle-stimulating hormone, hormone/choriogonadotropin receptor family from mammals
51. Activating mutations of the serotonin 5-HT2C receptor
52. i proteins in dual coupling of the luteinizing hormone receptor to adenylyl cyclase and phospholipase C
53. Effects of mutations involving the highly conserved S281HCC motif in the extracellular domain of the thyrotropin (TSH) receptor on TSH binding and constitutive activity
54. Three-dimensional models of gonado-thyrotropin hormone receptor transmembrane domain
55. Activating and inactivating mutations in N- and C-terminal i3 loop junctions of muscarinic acetylcholine Hm 1 receptors
56. Gonadotropin-independent precocious puberty
57. Adverse effects of luteinizing hormone on fertility: Fact or fantasy
58. The three subfamilies of leucine-rich repeat-containing G protein-coupled receptors (LGR): Identification of LGR6 and LGR7 and the signaling mechanism for LGR7
59. Identification of two amino acid residues on the extracellular domain of the lutropin/choriogonadotropin receptor important for signaling
60. Functional role of a conserved motif in TM6 of the rat mu opioid receptor: Constitutively active and inactive receptors result from substitutions of Thr6.34(279) with Lys and Asp
61. Substitution of M398T in the second transmembrane helix of the LH receptor in a patient with familial male-limited precocious puberty
62. sα in patients with gain and loss of endocrine function
63. Helix packing in polytopic membrane proteins: Role of glycine in transmembrane helix association
64. 2 adrenergic receptor alters the orientation of its sixth membrane-spanning segment
65. Agonist-induced conformational changes at the cytoplasmic side of transmembrane segment 6 in the beta 2 adrenergic receptor mapped by site-selective fluorescent labeling
66. G protein-coupled receptors I. Diversity of receptor-ligand interactions
67. Large kindred with male-limited precocious puberty associated with C581R mutation of LH-choriogonadotropin receptor gene
68. Identification of constitutively activating mutation of the luteinising hormone receptor in a family with male limited gonadotropin independent precocious puberty (testotoxicosis)
69. Agonist-specific receptor conformations
70. Regulation of thyroid cell proliferation by TSH and other factors: A critical evaluation of in vitro models
71. Insertional mutagenesis of the arginine cage domain of the gonadotrophin-releasing hormone receptor
72. 1B-adrenergic receptor by all amino acid substitutions at a single site: Evidence for a region which constrains receptor activation
73. The TSH receptor and its role in thyroid disease
74. A novel activating mutation in the thyrotropin receptor gene in an autonomously functioning thyroid nodule developed by a Japanese patient
75. Evidence that interhelical hydrogen bonding between Asp 578 and Asn 619 helps maintain the inactive conformation of the human lutropin receptor (LHR)
76. Constitutive activation of the thyrotropin receptor by mutating CYS-636 in the sixth transmembrane segment
77. 578 in maintaining the inactive conformation of the human lutropin/choriogonadotropin receptor
78. An anionic residue at position 564 is important for maintaining the inactive conformation of the human lutropin/chroiogonadotropin receptor
79. Characterization of heterozygous mutations causing constitutive activation of the luteinizing hormone receptor in familial male precocious puberty
80. A missense mutation in the second transmembrane segment of the luteinizing hormone receptor causes familial male-limited precocious puberty
81. Cosegregation of missense mutations of the luteinizing hormone receptor gene with familial male-limited precocious puberty
82. A limited repertoire of mutations of the luteinizing hormone (LH) receptor gene in familial and sporadic patients with male LH-independent precocious puberty
83. 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
84. Transmembrane regions V and VI of the human luteinizing hormone receptor are required for constitutive activation by a mutation in the third intracellular loop
85. The luteinizing hormone receptor activates phospholipase C via preferential coupling to Gi2
86. A refined model of the thyrotropin-releasing hormone (TRH) receptor binding pocket. Novel mixed mode Monte Carlo/stochastic dynamics simulations of the complex between TRH and TRH receptor
87. Crystal structure of human chorionic gonadotropin
88. The effect of distinct activating mutations of the luteinizing hormone receptor gene on the pituitary-gonadal axis in both sexes
89. Naturally occurring mutations of the luteinizing-hormone receptor: Lessons learned about reproductive physiology and G protein-coupled receptors
90. Gonadotropin-independent precocious puberty due to luteinizing hormone receptor mutations in Brazilian boys: A novel constitutively activating mutation in the first transmembrane helix
91. A unique constitutively activating mutation in third transmembrane helix of luteinizing hormone receptor causes sporadic male gonadotropin-independent precocious puberty
92. A novel mutation of the luteinizing hormone receptor gene causing male gonadotropin-independent precocious puberty
93. Constitutively active mutants of the beta1-adrenergic receptor
94. Genetic heterogeneity of constitutively activating mutations of the human luteinizing hormone receptor in familial male-limited precocious puberty
95. Heterogeneity of activating mutations of the human luteinizing hormone receptor in male-limited precocious puberty
96. 1B-adrenergic receptor transgene promotes malignant transformation of thyroid follicular cells
97. Targeted disruption of luteinizing hormone/human chorionic gonadotropin receptor gene
98. Specificity and promiscuity in membrane helix interactions
99. Nodular Leydig cell hyperplasia in a boy with familial male-limited precocious puberty
100. Six-year results of spironolactone and testolactone treatment of familial male-limited precocious puberty with addition of deslorelin after central puberty onset
101. Familial male precocious puberty
102. A model of the lutropin/choriogonadotropin receptor: Insights into the structural and functional effects of constitutively activating mutations
103. Leydig-cell tumors caused by an activating mutation of the gene encoding the luteinizing hormone receptor
104. Comparative function of glycoprotein hormone receptors containing an activating aspartate to histidine substitution in transmembrane helix 6
105. Molecular characterization of a novel glycoprotein hormone G-protein-coupled receptor
106. The functional topography of transmembrane domain 3 of the M1 muscarinic acetylcholine receptor, revealed by scanning mutagenesis
107. A network of conserved intramolecular contacts defines the off-state of the transmembrane switch mechanism in a seven-transmembrane receptor
108. A transmembrane helix dimer: Structure and implications
109. A six-year-old boy with multiple bone lesions, repeated fractures, and sexual precocity
110. Control of conformational equilibria in the human B2 bradykinin receptor: Modeling of nonpeptidic ligand action and comparison to the rhodopsin structure
111. Testicular seminoma in a patient with a constitutively activating mutation of the luteinizing hormone/chorionic gonadotropin receptor
112. Identification and cloning of an orphan G protein-coupled receptor of the glycoprotein hormone receptor subfamily
113. Rhodopsin: Structural basis of molecular physiology
114. Effect of activating and inactivating mutations on the phosphorylation and trafficking of the human lutropin/choriogonadotropin receptor
115. The association of arrestin-3 with the human lutropin/choriogonadotropin receptor depends mostly on receptor activation rather than on receptor phosphorylation
116. Gonadotropin receptors and the control of gonadal steroidogenesis: Physiology and pathology
117. Model of human chorionic gonadotropin and lutropin receptor interaction that explains signal transduction of the glycoprotein hormones
118. Severe testotoxicosis phenotype associated with Asp578 to Tyr mutation of the lutrophin/choriogonadotropin receptor gene
119. A free carboxylate oxygen in the side chain of position 674 in transmembrane domain 7 is necessary for TSH receptor activation
120. Chronic hypersecretion of luteinizing hormone in transgenic mice disrupts both ovarian and pituitary function, with some effects modified by the genetic background
121. The ectodomain of the luteinizing hormone receptor interacts with exoloop 2 to constrain the transmembrane region: Studies using chimeric human and fly receptors
122. Molecular cloning of a novel, putative G protein-coupled receptor from sea anemones structurally related to members of the FSH, TSH, LH/CG receptor family from mammals
123. Activation of rhodopsin: New insights from structural and biochemical studies
124. Crystal structure of rhodopsin: Implications for vision and beyond
125. Agonist efficacy and allosteric models of receptor action
126. Crystal structure of rhodopsin: A G protein-coupled receptor
127. Mutations of two adjacent amino acids generate inactive and constitutively active forms of the human platelet-activating factor receptor
128. sα genes as a cause of toxic thyroid adenomas
129. Systematic identification of mutations that constitutively activate the angiotensin II type 1A receptor by screening a randomly mutated cDNA library with an original pharmacological bioassay
130. Constitutive activation of a single effector pathway: Evidence for multiple activation states of a G protein-coupled receptor
131. Influence of a lysine 331 counterion on the pK(a) of aspartic acid 125: Evidence for a salt-bridge interaction and role in alpha(1b)-adrenergic receptor activation
132. Incomplete clinical penetrance of the activating M398T mutation in helix 2 of the luteinizing hormone receptor (LHR)
133. Activating mutations of rhodopsin and other G protein-coupled receptors
134. 2-adrenergic receptor
135. Non-alpha-helical elements modulate polytopic membrane protein architecture
136. Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function
137. Constitutively active mutants of rhodopsin
138. Conserved helix 7 tyrosine functions as an activation relay in the serotonin 5HT(2C) receptor
139. Response to challenge with gonadotropin-releasing hormone agonist in a mother and her two sons with a constitutively activating mutation of the luteinizing hormone receptor
140. Gonadotropin-independent familial sexual precocity with premature Leydig and germinal cell maturation (familial testotoxicosis): Effects of a potent luteinizing hormone-releasing factor agonist and therapy in four cases
141. Inverse agonism and neutral antagonism at alpha(1a)- and alpha(1b)- adrenergic receptor subtypes
142. The GxxxG motif: A framework for transmembrane helix-helix association
143. Detection of an activating mutation of the thyrotropin receptor in a case of an autonomously hyperfunctioning thyroid insular carcinoma
144. 2-adrenergic receptor: Extending the ternary complex model
145. Hinges, swivels and switches: The role of prolines in signalling via transmembrane alpha-helices
146. 1B-adrenergic receptor: Potential role of protonation and hydrophobicity of a highly conserved aspartate
147. Requirement of specific intrahelical interactions for stabilizing the inactive conformation of glycoprotein hormone receptors
148. Role of the third intracellular loop for the activation of gonadotropin receptors
149. Is there a 'lock' for all agonist 'keys' in 7TM receptors?
150. Testicular tumors with endocrine manifestations
151. The lutropin/choriogonadotropin receptor...4 years later
152. Similar structures and shared switch mechanisms of the beta2- adrenoceptor and the parathyroid hormone receptor. Zn(II) bridges between helices III and VI block activation
153. Rhodopsin activation blocked by metal-ion-binding sites linking transmembrane helices C and F
154. A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty
155. Japanese familial patients with male-limited precocious puberty
156. Pleiotropic effects of substitutions of a highly conserved leucine in transmembrane helix III of the human lutropin/choriogonadotropin receptor with respect to constitutive activation and hormone responsiveness
157. Human chorionic gonadotropin-secreting pineal tumor: Relation to pathogenesis and sex limitation of sexual precocity
158. Identification of a ligand-dependent switch within a muscarinic receptor
159. Extraordinary precocity in the development of the male sexual organs and muscular system in a child four years old
160. Recruitment of individually (all-or-none) responding cells, rather than amplitude enhancement, is the single-cell mechanism subserving the dose-responsive activation of intracellular calcium second messenger luteinizing-hormone receptor
161. Constitutive activation of G protein-coupled receptors as a result of selective substitution of a conserved leucine residue in transmembrane helix III
162. An aspartate VI:12 to glycine mutation in the rat, but not the human, FSHR causes constitutive activity: Identification of two transmembrane residues which "permit" or "suppress" constitutive activation of the mutation
163. Advances in determination of a high-resolution three-dimensional structure of rhodopsin, a model of G-protein-coupled receptors (GPCRs)
164. A G protein-coupled receptor with low density lipoprotein-binding motifs suggests a role for lipoproteins in G-linked signal transduction
165. Mutations of gonadotropins and gonadotropin receptors: Elucidating the physiology and pathophysiology of pituitary-gonadal function
166. 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
167. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome
168. Molecular basis of receptor/G-protein-coupling selectivity
169. Mechanisms of inverse agonism of antipsychotic drugs at the D(2) dopamine receptor: Use of a mutant D(2) dopamine receptor that adopts the activated conformation
170. Luteinizing hormone receptor mutations in disorders of sexual development and cancer
171. A novel luteinizing hormone receptor mutation in a patient with familial male-limited precocious puberty: Effect of the size of a critical amino acid on receptor activity
172. A sporadic case of male-limited precocious puberty has the same constitutively activating point mutation in luteinizing hormone/choriogonadotropin receptor gene as familial cases
173. Phe576 plays an important role in the secondary structure and intracellular signaling of the human luteinizing hormone/chorionic gonadotropin receptor
174. A case of male-limited precocious puberty caused by a point mutation in the second transmembrane domain of the luteinizing hormone choriogonadotropin receptor gene
175. A new constitutively activating point mutation in the luteinizing hormone/choriogonadotropin receptor gene in cases of male-limited precocious puberty
176. The role of the hinge region of the luteinizing hormone receptors in hormone interaction and signal generation
177. Normal prenatal but arrested postnatal sexual development of luteinizing hormone receptor knockout (LuRKO) mice
178. The extracellular domain suppresses constitutive activity of the transmembrane domain of the human TSH receptor: Implications for hormone-receptor interaction and antagonist design
179. 2-adrenergic receptor