Cases of Borderline in Vitro Constitutive Thyrotropin Receptor Activity: How to Decide Whether a Thyrotropin Receptor Mutation Is Constitutively Active or Not?
dc.authorid | 0000-0001-5291-8620 | |
dc.authorid | 0000-0002-4732-2934 | |
dc.authorscopusid | 15070736900 | |
dc.authorscopusid | 16241650400 | |
dc.authorscopusid | 8416126500 | |
dc.authorscopusid | 9275130900 | |
dc.authorscopusid | 57195256086 | |
dc.authorscopusid | 29067965900 | |
dc.authorscopusid | 7202378037 | |
dc.authorwosid | Bircan, Rıfat/A-7344-2018 | |
dc.contributor.author | Mueller, Sandra | |
dc.contributor.author | Gözü, Hülya İliksu | |
dc.contributor.author | Bircan, Rifat | |
dc.contributor.author | Jaeschke, Holger | |
dc.contributor.author | Eszlinger, Markus | |
dc.contributor.author | Lueblinghoff, Julia | |
dc.contributor.author | Paschke, Ralf | |
dc.date.accessioned | 2022-05-11T14:28:24Z | |
dc.date.available | 2022-05-11T14:28:24Z | |
dc.date.issued | 2009 | |
dc.department | Fakülteler, Fen Edebiyat Fakültesi, Biyoloji Bölümü | |
dc.description.abstract | Background: Previous in vitro data for several constitutively activating thyrotropin receptor (TSHR) mutations reported divergent results for the constitutive activity of the same mutations. Moreover, several case reports have highlighted the difficulties in determining whether a TSHR mutation is constitutively active or not. Retrospectively, this has repeatedly been the case for mutants with only a slight increase of basal cAMP activity. We re-examined 10 previously described TSHR germline mutations with minor increases of basal cAMP activity and analyzed the influences of the cell line and vector system on the basal receptor activity. Methods: TSHR mutations were characterized by determination of cell surface expression, cAMP accumulation, and linear regression analysis of constitutive activity. Results: Re-examination of the previously described constitutively active TSHR germline mutations did not show constitutive activity for R310C and N670S as tested in COS-7 cells and confirmed constitutive activity for the other eight mutations. However, mutant N670S showed a slight but significant increase of basal activity measured by linear regression analysis when analyzed in HEKGT cells transiently transfected with pcDNA but not with the pSVL vector. This was not the case for R310C. Conclusions: Our findings indicate that current methods to precisely classify mutants with only a slight increase of the basal activity as constitutively active are limited. The results concerning the level of the basal activity can be influenced by the vector and/or the cell system. A comprehensive clinical characterization of the respective patients appears as a necessary and promising adjunct for the activity classification of these borderline mutations. | |
dc.description.sponsorship | Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [DFG/Pa 423/14-1] | |
dc.description.sponsorship | We thank Eileen Boesenberg and Saskia Fiedler (Department of Internal Medicine III, University of Leipzig, D-04103 Leipzig, Germany) for her excellent technical assistance and Micheline Misrahi (Laboratory of Molecular Genetics, Pharmacology and Hormones, University of Paris, France) and Susanne Neumann (Clinical Endocrinology Branch, NIDDK, National Institutes of Health, Bethesda, MD) for critical reading of the manuscript. This work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG/Pa 423/14-1). | |
dc.identifier.doi | 10.1089/thy.2009.0006 | |
dc.identifier.endpage | 773 | |
dc.identifier.issn | 1050-7256 | |
dc.identifier.issn | 1557-9077 | |
dc.identifier.issue | 7 | en_US |
dc.identifier.pmid | 19583488 | |
dc.identifier.scopus | 2-s2.0-67749131205 | |
dc.identifier.scopusquality | Q1 | |
dc.identifier.startpage | 765 | |
dc.identifier.uri | https://doi.org/10.1089/thy.2009.0006 | |
dc.identifier.uri | https://hdl.handle.net/20.500.11776/6810 | |
dc.identifier.volume | 19 | |
dc.identifier.wos | WOS:000267762900012 | |
dc.identifier.wosquality | Q3 | |
dc.indekslendigikaynak | Web of Science | |
dc.indekslendigikaynak | Scopus | |
dc.indekslendigikaynak | PubMed | |
dc.institutionauthor | Bircan, Rifat | |
dc.language.iso | en | |
dc.publisher | Mary Ann Liebert, Inc | |
dc.relation.ispartof | Thyroid | |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.rights | info:eu-repo/semantics/closedAccess | |
dc.subject | Autosomal-Dominant Hyperthyroidism | |
dc.subject | Hyperfunctioning Thyroid Adenomas | |
dc.subject | Stimulating Hormone-Receptor | |
dc.subject | Tsh Receptor | |
dc.subject | Germline Mutation | |
dc.subject | Somatic Mutations | |
dc.subject | Nonautoimmune Hyperthyroidism | |
dc.subject | Transmembrane Domain | |
dc.subject | Extracellular Domain | |
dc.subject | Congenital Hyperthyroidism | |
dc.title | Cases of Borderline in Vitro Constitutive Thyrotropin Receptor Activity: How to Decide Whether a Thyrotropin Receptor Mutation Is Constitutively Active or Not? | |
dc.type | Article |
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