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Sci. Signal., 9 August 2011
Vol. 4, Issue 185, p. ra51
[DOI: 10.1126/scisignal.2001707]

RESEARCH ARTICLES

Editor's Summary

Cracking a Phosphorylation Code
Not only can ligands for G protein–coupled receptors (GPCRs) trigger signaling through two completely different pathways—G protein–mediated and β-arrestin–mediated—Nobles et al. report that phosphorylation of one of these receptors, the β2-adrenergic receptor, by isoform-specific GPCR kinases (GRKs) produces distinct phosphorylation patterns that influence β-arrestin conformation and induce distinct downstream responses. As noted in the Perspective by Liggett, GPCRs are the largest class of signaling proteins in the human genome and are common targets of clinically used therapeutic agents. Drugs that bias signaling down G protein–coupled pathways or the β-arrestin pathways already exist. That the β-arrestin pathways depend on the specific GRK-induced "barcode" triggered by receptor activation has implications for understanding the effects of existing drugs and the development of selective therapies targeting specific β-arrestin–mediated pathways.

Citation: K. N. Nobles, K. Xiao, S. Ahn, A. K. Shukla, C. M. Lam, S. Rajagopal, R. T. Strachan, T.-Y. Huang, E. A. Bressler, M. R. Hara, S. K. Shenoy, S. P. Gygi, R. J. Lefkowitz, Distinct Phosphorylation Sites on the β2-Adrenergic Receptor Establish a Barcode That Encodes Differential Functions of β-Arrestin. Sci. Signal. 4, ra51 (2011).

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