Title
Informatic deconvolution of biased GPCR signaling mechanisms from in vivo pharmacological experimentation Informatic deconvolution of biased GPCR signaling mechanisms from in vivo pharmacological experimentation
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
San Diego, Calif. ,
Subject
Chemistry
Biology
Human medicine
Source (journal)
Methods: a companion to methods in enzymology. - San Diego, Calif.
Volume/pages
92(2016) , p. 51-63
ISSN
1046-2023
ISI
000368212500006
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Ligands possessing different physico-chemical structures productively interact with G protein-coupled receptors generating distinct downstream signaling events due to their abilities to activate/select idiosyncratic receptor entities (receptorsomes) from the full spectrum of potential receptor partners. We have employed multiple novel informatic approaches to identify and characterize the in vivo transcriptomic signature of an arrestin-signaling biased ligand, [D-Trp12,Tyr34]-bPTH(7-34), acting at the parathyroid hormone type 1 receptor (PTH1R), across six different murine tissues after chronic drug exposure. We are able to demonstrate that [D-Trp12,Tyr34]-bPTH(7-34) elicits a distinctive arrestin-signaling focused transcriptomic response that is more coherently regulated, in an arrestin signaling-dependent manner, across more tissues than that of the pluripotent endogenous PTH1R ligand, hPTH(1-34). This arrestin-focused response signature is strongly linked with the transcriptional regulation of cell growth and development. Our informatic deconvolution of a conserved arrestin-dependent transcriptomic signature from wild type mice demonstrates a conceptual framework within which the in vivo outcomes of biased receptor signaling may be further investigated or predicted.
E-info
https://repository.uantwerpen.be/docman/iruaauth/c69cf2/128013.pdf
Full text (open access)
https://repository.uantwerpen.be/docman/irua/ef204e/128013.pdf
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