FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2023288129> ?p ?o ?g. }

• W2023288129 endingPage "3517" @default.
• W2023288129 startingPage "3514" @default.
• W2023288129 abstract "Among glycoprotein hormone receptors the TSH receptor (TSHR) is the most susceptible to constitutive activation by mutations in various regions of the molecule, including mutations in the extracellular domain (ECD) and extracellular loops of the transmembrane domain (TMD). To understand the role of the ECD in TSHR activation we have tested several TSHR constructs with major deletions of the ECD. Previous studies reported very low expression of such truncated glycoprotein hormone receptors, which prevented reliable assessment of their ligand-binding and basal constitutive activities. We have eliminated this problem using TSHR tagged at its N-terminus with a hemagglutinin tag (HA) recognized by the HA-specific monoclonal antibody. Based on such quantitation the TSHR deletion mutant missing 386 N-terminal amino acid residues, constituting 98% of the entire ECD, showed 4-7 fold higher normalized basal activity compared to activity of the corresponding wild-type (WT) TSHR construct. This increase in basal activity was significantly inhibited by linking the common alpha-subunit of glycoprotein hormones at the N-terminus of the truncated TSH receptor. The role of a hypothetical activating fragment (409-418) in TSHR activation was further studied using peptides and mutagenesis of charged residues. This study provides important evidence supporting the two-state model of TSHR activation and the potential role of proteolytic cleavage for receptor activation. Accordingly, the mechanism of hormone-induced receptor activation is dependent, at least in part, on the elimination of inhibitory interactions within the receptor. Such intra-molecular inhibition of TSHR may include electrostatic interactions between the ECD and extracellular loops of TMD. Moreover, the truncated, constitutively active receptors described herein provide new insights valuable in the design of TSHR antagonists." @default.
• W2023288129 created "2016-06-24" @default.
• W2023288129 creator A5031319152 @default.
• W2023288129 creator A5052589187 @default.
• W2023288129 creator A5058033450 @default.
• W2023288129 creator A5058522048 @default.
• W2023288129 creator A5073329018 @default.
• W2023288129 creator A5074140059 @default.
• W2023288129 creator A5081348634 @default.
• W2023288129 creator A5086131245 @default.
• W2023288129 date "2000-09-01" @default.
• W2023288129 modified "2023-10-16" @default.
• W2023288129 title "The Extracellular Domain Suppresses Constitutive Activity of the Transmembrane Domain of the Human TSH Receptor: Implications for Hormone-Receptor Interaction and Antagonist Design" @default.
• W2023288129 doi "https://doi.org/10.1210/endo.141.9.7790" @default.
• W2023288129 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10965926" @default.
• W2023288129 hasPublicationYear "2000" @default.
• W2023288129 type Work @default.
• W2023288129 sameAs 2023288129 @default.
• W2023288129 citedByCount "121" @default.
• W2023288129 countsByYear W20232881292012 @default.
• W2023288129 countsByYear W20232881292013 @default.
• W2023288129 countsByYear W20232881292014 @default.
• W2023288129 countsByYear W20232881292015 @default.
• W2023288129 countsByYear W20232881292016 @default.
• W2023288129 countsByYear W20232881292017 @default.
• W2023288129 countsByYear W20232881292018 @default.
• W2023288129 countsByYear W20232881292019 @default.
• W2023288129 countsByYear W20232881292020 @default.
• W2023288129 countsByYear W20232881292021 @default.
• W2023288129 countsByYear W20232881292022 @default.
• W2023288129 countsByYear W20232881292023 @default.
• W2023288129 crossrefType "journal-article" @default.
• W2023288129 hasAuthorship W2023288129A5031319152 @default.
• W2023288129 hasAuthorship W2023288129A5052589187 @default.
• W2023288129 hasAuthorship W2023288129A5058033450 @default.
• W2023288129 hasAuthorship W2023288129A5058522048 @default.
• W2023288129 hasAuthorship W2023288129A5073329018 @default.
• W2023288129 hasAuthorship W2023288129A5074140059 @default.
• W2023288129 hasAuthorship W2023288129A5081348634 @default.
• W2023288129 hasAuthorship W2023288129A5086131245 @default.
• W2023288129 hasBestOaLocation W20232881291 @default.
• W2023288129 hasConcept C1009742 @default.
• W2023288129 hasConcept C104317684 @default.
• W2023288129 hasConcept C108625454 @default.
• W2023288129 hasConcept C118892022 @default.
• W2023288129 hasConcept C121608353 @default.
• W2023288129 hasConcept C126322002 @default.
• W2023288129 hasConcept C133603901 @default.
• W2023288129 hasConcept C134018914 @default.
• W2023288129 hasConcept C143065580 @default.
• W2023288129 hasConcept C16318435 @default.
• W2023288129 hasConcept C170493617 @default.
• W2023288129 hasConcept C185592680 @default.
• W2023288129 hasConcept C23589133 @default.
• W2023288129 hasConcept C2776652619 @default.
• W2023288129 hasConcept C2777608072 @default.
• W2023288129 hasConcept C28406088 @default.
• W2023288129 hasConcept C526584372 @default.
• W2023288129 hasConcept C530470458 @default.
• W2023288129 hasConcept C55493867 @default.
• W2023288129 hasConcept C71924100 @default.
• W2023288129 hasConcept C86803240 @default.
• W2023288129 hasConcept C95444343 @default.
• W2023288129 hasConceptScore W2023288129C1009742 @default.
• W2023288129 hasConceptScore W2023288129C104317684 @default.
• W2023288129 hasConceptScore W2023288129C108625454 @default.
• W2023288129 hasConceptScore W2023288129C118892022 @default.
• W2023288129 hasConceptScore W2023288129C121608353 @default.
• W2023288129 hasConceptScore W2023288129C126322002 @default.
• W2023288129 hasConceptScore W2023288129C133603901 @default.
• W2023288129 hasConceptScore W2023288129C134018914 @default.
• W2023288129 hasConceptScore W2023288129C143065580 @default.
• W2023288129 hasConceptScore W2023288129C16318435 @default.
• W2023288129 hasConceptScore W2023288129C170493617 @default.
• W2023288129 hasConceptScore W2023288129C185592680 @default.
• W2023288129 hasConceptScore W2023288129C23589133 @default.
• W2023288129 hasConceptScore W2023288129C2776652619 @default.
• W2023288129 hasConceptScore W2023288129C2777608072 @default.
• W2023288129 hasConceptScore W2023288129C28406088 @default.
• W2023288129 hasConceptScore W2023288129C526584372 @default.
• W2023288129 hasConceptScore W2023288129C530470458 @default.
• W2023288129 hasConceptScore W2023288129C55493867 @default.
• W2023288129 hasConceptScore W2023288129C71924100 @default.
• W2023288129 hasConceptScore W2023288129C86803240 @default.
• W2023288129 hasConceptScore W2023288129C95444343 @default.
• W2023288129 hasIssue "9" @default.
• W2023288129 hasLocation W20232881291 @default.
• W2023288129 hasLocation W20232881292 @default.
• W2023288129 hasOpenAccess W2023288129 @default.
• W2023288129 hasPrimaryLocation W20232881291 @default.
• W2023288129 hasRelatedWork W1988275891 @default.
• W2023288129 hasRelatedWork W2022797453 @default.
• W2023288129 hasRelatedWork W2023288129 @default.
• W2023288129 hasRelatedWork W2034543483 @default.
• W2023288129 hasRelatedWork W2048350316 @default.
• W2023288129 hasRelatedWork W2087679426 @default.
• W2023288129 hasRelatedWork W2321550529 @default.
• W2023288129 hasRelatedWork W2329528152 @default.

• next