@article {Maudsley706, author = {Maudsley, Stuart and Martin, Bronwen and Gesty-Palmer, Diane and Cheung, Huey and Johnson, Calvin and Patel, Shamit and Becker, Kevin G. and Wood, William H. and Zhang, Yongqing and Lehrmann, Elin and Luttrell, Louis M.}, title = {Delineation of a Conserved Arrestin-Biased Signaling Repertoire In Vivo}, volume = {87}, number = {4}, pages = {706--717}, year = {2015}, doi = {10.1124/mol.114.095224}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Biased G protein{\textendash}coupled receptor agonists engender a restricted repertoire of downstream events from their cognate receptors, permitting them to produce mixed agonist-antagonist effects in vivo. While this opens the possibility of novel therapeutics, it complicates rational drug design, since the in vivo response to a biased agonist cannot be reliably predicted from its in cellula efficacy. We have employed novel informatic approaches to characterize the in vivo transcriptomic signature of the arrestin pathway-selective parathyroid hormone analog [d-Trp12, Tyr34]bovine PTH(7-34) in six different murine tissues after chronic drug exposure. We find that [d-Trp12, Tyr34]bovine PTH(7-34) elicits a distinctive arrestin-signaling focused transcriptomic response that is more coherently regulated across tissues than that of the pluripotent agonist, human PTH(1-34). This arrestin-focused network is closely associated with transcriptional control of cell growth and development. Our demonstration of a conserved arrestin-dependent transcriptomic signature suggests a framework within which the in vivo outcomes of arrestin-biased signaling may be generalized.}, issn = {0026-895X}, URL = {http://molpharm.aspetjournals.org/content/87/4/706}, eprint = {http://molpharm.aspetjournals.org/content/87/4/706.full.pdf}, journal = {Molecular Pharmacology} }