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Molecular Pharmacology

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Research ArticleArticle

Delineation of a Conserved Arrestin-Biased Signaling Repertoire In Vivo

Stuart Maudsley, Bronwen Martin, Diane Gesty-Palmer, Huey Cheung, Calvin Johnson, Shamit Patel, Kevin G. Becker, William H. Wood, Yongqing Zhang, Elin Lehrmann and Louis M. Luttrell
Molecular Pharmacology January 30, 2015, mol.114.095224; DOI: https://doi.org/10.1124/mol.114.095224
Stuart Maudsley
1 University of Antwerp;
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Bronwen Martin
2 NIH National Institute on Aging;
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Diane Gesty-Palmer
3 Duke University Medical Center;
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Huey Cheung
4 NIH Center for Information Technology;
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Calvin Johnson
4 NIH Center for Information Technology;
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Shamit Patel
2 NIH National Institute on Aging;
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Kevin G. Becker
2 NIH National Institute on Aging;
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William H. Wood
2 NIH National Institute on Aging;
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Yongqing Zhang
2 NIH National Institute on Aging;
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Elin Lehrmann
5 NIH National Institue on Aging;
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Louis M. Luttrell
6 Medical University of South Carolina
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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.

  • Arrestins
  • GRKs, barrestins
  • Pharmacogenomic analyses
  • Signaling network analyses
  • Regulation of gene expression
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 103 (2)
Molecular Pharmacology
Vol. 103, Issue 2
1 Feb 2023
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Research ArticleArticle

Delineation of a Conserved Arrestin-Biased Signaling Repertoire In Vivo

Stuart Maudsley, Bronwen Martin, Diane Gesty-Palmer, Huey Cheung, Calvin Johnson, Shamit Patel, Kevin G. Becker, William H. Wood, Yongqing Zhang, Elin Lehrmann and Louis M. Luttrell
Molecular Pharmacology January 30, 2015, mol.114.095224; DOI: https://doi.org/10.1124/mol.114.095224

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Research ArticleArticle

Delineation of a Conserved Arrestin-Biased Signaling Repertoire In Vivo

Stuart Maudsley, Bronwen Martin, Diane Gesty-Palmer, Huey Cheung, Calvin Johnson, Shamit Patel, Kevin G. Becker, William H. Wood, Yongqing Zhang, Elin Lehrmann and Louis M. Luttrell
Molecular Pharmacology January 30, 2015, mol.114.095224; DOI: https://doi.org/10.1124/mol.114.095224
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