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Delineation of a conserved arrestin-biased signaling repertoire in vivo

ABSTRACT: 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 vitro 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]-bPTH(7-34) in six different murine tissues after chronic drug exposure. We find that [D-Trp12, Tyr34]-bPTH(7-34) elicits a distinctive arrestin-signaling focused transcriptomic response that is more coherently regulated across tissues than that of the pluripotent agonist, hPTH(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.

ORGANISM(S): Mus musculus

PROVIDER: GSE64485 | GEO | 2015/03/05

SECONDARY ACCESSION(S): PRJNA271097

REPOSITORIES: GEO

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beta-Arrestin Pathway-Selective G Protein-Coupled Receptor Agonists Engender Unique Biological Efficacy In Vivo

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Mus musculus

Project description:Delineation of a conserved arrestin-biased signaling repertoire in vivo

| PRJNA271097 | ENA

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