%0 Journal Article
%T Biased Signaling of the Angiotensin II Type 1 Receptor Can Be Mediated through Distinct Mechanisms
%A Marie Mi Bonde
%A Jonas Tind Hansen
%A Samra Joke Sanni
%A Stig Hauns£¿
%A Steen Gammeltoft
%A Christina Lyngs£¿
%A Jakob Lerche Hansen
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0014135
%X Seven transmembrane receptors (7TMRs) can adopt different active conformations facilitating a selective activation of either G protein or ¦Â-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 ¦Â-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 ¦Â-arrestins. Since uncoupling of G proteins by increased ability to recruit ¦Â-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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0014135