TY - JOUR T1 - Delineation of a Conserved Arrestin-Biased Signaling Repertoire In Vivo JF - Molecular Pharmacology JO - Mol Pharmacol SP - 706 LP - 717 DO - 10.1124/mol.114.095224 VL - 87 IS - 4 AU - Stuart Maudsley AU - Bronwen Martin AU - Diane Gesty-Palmer AU - Huey Cheung AU - Calvin Johnson AU - Shamit Patel AU - Kevin G. Becker AU - William H. Wood III AU - Yongqing Zhang AU - Elin Lehrmann AU - Louis M. Luttrell Y1 - 2015/04/01 UR - http://molpharm.aspetjournals.org/content/87/4/706.abstract N2 - Biased G protein–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. ER -