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Biased signaling of the angiotensin II type 1 receptor can be mediated through distinct mechanisms

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Marie Mi Bonde
  • Jonas Tind Hansen
  • Samra Joke Sanni
  • Steen Gammeltoft
  • Stig Haunsø
  • Christina Lyngsø
  • Jakob Lerche Hansen
Seven transmembrane receptors (7TMRs) can adopt different active conformations facilitating a selective activation of either G protein or ß-arrestin-dependent signaling pathways. This represents an opportunity for development of novel therapeutics targeting selective biological effects of a given receptor. Several studies on pathway separation have been performed, many of these on the Angiotensin II type 1 receptor (AT1R). It has been shown that certain ligands or mutations facilitate internalization and/or recruitment of ß-arrestins without activation of G proteins. However, the underlying molecular mechanisms remain largely unresolved. For instance, it is unclear whether such selective G protein-uncoupling is caused by a lack of ability to interact with G proteins or rather by an increased ability of the receptor to recruit ß-arrestins. Since uncoupling of G proteins by increased ability to recruit ß-arrestins could lead to different cellular or in vivo outcomes than lack of ability to interact with G proteins, it is essential to distinguish between these two mechanisms.
OriginalsprogEngelsk
TidsskriftP L o S One
Vol/bind5
Udgave nummer11
Sider (fra-til)e14135
ISSN1932-6203
DOI
StatusUdgivet - 1 jan. 2010

ID: 34168040