WeightNameValue
1000 Titel
  • 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
1000 Autor/in
  1. Mueller, Sandra |
  2. Kleinau, Gunnar |
  3. Szkudlinski, Mariusz W. |
  4. Jaeschke, Holger |
  5. Krause, Gerd |
  6. Paschke, Ralf |
1000 Erscheinungsjahr 2009
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2009-04-22
1000 Erschienen in
1000 Quellenangabe
  • 284: 16317-16324
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713536/ |
  • http://doi.org/10.1074/jbc.M109.005710 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Bovine TSH (bTSH) has a higher affinity to the human TSHR (hTSHR) and a higher signaling activity than human TSH (hTSH). The molecular reasons for these phenomena are unknown. Distinct negatively charged residues (Glu297, Glu303, and Asp382) in the hinge region of the hTSHR are known to be important for bTSH binding and signaling. To investigate the potential relevance of these positions for differences between bTSH and hTSH in the interaction to the hTSHR, we determined bTSH- and hTSH-mediated cAMP production of several substitutions at these three hinge residues. To examine specific variations of hTSH, we also investigated the superagonistic hTSH analog TR1401 (TR1401), whose sequence differs from hTSH by four additional positively charged amino acids that are also present in bTSH. To characterize possible interactions between the acidic hTSHR positions Glu297, Glu303, or Asp382 and the additional basic residues of TR1401, we investigated TR1401 binding and signaling properties. Our data reveal increased cAMP signaling of the hTSHR using TR1401 and bTSH compared with hTSH. Whereas Asp382 seems to be important for bTSH- and TR1401-mediated but not for hTSH-mediated signaling, the substitution E297K exhibits a decreased signaling for all three TSH variants. Interestingly, bTSH and TR1401 showed only a slightly different binding pattern. These observations imply that specific residues of the hinge region are mediators of the superagonistic activity of bTSH and TR1401 in contrast to hTSH. Moreover, the simultaneous localization of binding components in the glycoprotein hormone molecule and the receptor hinge region permits important reevaluation of interacting hormone receptor domains.
1000 Fachgruppe
  1. Biologie |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/TXVlbGxlciwgU2FuZHJh|https://frl.publisso.de/adhoc/creator/S2xlaW5hdSwgR3VubmFy|https://frl.publisso.de/adhoc/creator/U3prdWRsaW5za2ksIE1hcml1c3ogVy4=|https://frl.publisso.de/adhoc/creator/SmFlc2Noa2UsIEhvbGdlcg==|https://frl.publisso.de/adhoc/creator/S3JhdXNlLCBHZXJk|https://frl.publisso.de/adhoc/creator/UGFzY2hrZSwgUmFsZg==
1000 Förderer
  1. Deutsche Forschungsgemeinschaft |
1000 Fördernummer
  1. KR 1223/1-2; PA 42312-2
1000 Förderprogramm
  1. -
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer KR 1223/1-2; PA 42312-2
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6403009.rdf
1000 Erstellt am 2017-06-13T10:48:46.816+0200
1000 Erstellt von 25
1000 beschreibt frl:6403009
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Wed Aug 01 11:44:09 CEST 2018
1000 Objekt bearb. Wed Aug 01 11:44:08 CEST 2018
1000 Vgl. frl:6403009
1000 Oai Id
  1. oai:frl.publisso.de:frl:6403009 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
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