Abstract
G protein-coupled receptors (GPCRs) are a family of cell-surface proteins that play critical roles in regulating a variety of pathophysiological processes and thus are targeted by almost a third of currently available therapeutics. It was originally thought that GPCRs convert extracellular stimuli into intracellular signals through activating G proteins, whereas β-arrestins have important roles in internalization and desensitization of the receptor. Over the past decade, several novel functional aspects of β-arrestins in regulating GPCR signaling have been discovered. These previously unanticipated roles of β-arrestins to act as signal transducers and mediators of G protein-independent signaling have led to the concept of biased agonism. Biased GPCR ligands are able to engage with their target receptors in a manner that preferentially activates only G protein- or β-arrestin-mediated downstream signaling. This offers the potential for next generation drugs with high selectivity to therapeutically relevant GPCR signaling pathways. In this review, we provide a summary of the recent studies highlighting G protein- or β-arrestin-biased GPCR signaling and the effects of biased ligands on disease pathogenesis and regulation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 12-25 |
| Number of pages | 14 |
| Journal | Biomolecules and Therapeutics |
| Volume | 25 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2017 |
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Keywords
- Biased signaling
- G protein
- G protein-coupled receptor
- β-arrestin
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Pharmacology
- Drug Discovery
Cite this
Biased g protein-coupled receptor signaling : New player in modulating physiology and pathology. / Bologna, Zuzana; Teoh, Jian Peng; Bayoumi, Ahmed S.; Tang, Yao Liang; Kim, Il-man.
In: Biomolecules and Therapeutics, Vol. 25, No. 1, 01.01.2017, p. 12-25.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Biased g protein-coupled receptor signaling
T2 - New player in modulating physiology and pathology
AU - Bologna, Zuzana
AU - Teoh, Jian Peng
AU - Bayoumi, Ahmed S.
AU - Tang, Yao Liang
AU - Kim, Il-man
PY - 2017/1/1
Y1 - 2017/1/1
N2 - G protein-coupled receptors (GPCRs) are a family of cell-surface proteins that play critical roles in regulating a variety of pathophysiological processes and thus are targeted by almost a third of currently available therapeutics. It was originally thought that GPCRs convert extracellular stimuli into intracellular signals through activating G proteins, whereas β-arrestins have important roles in internalization and desensitization of the receptor. Over the past decade, several novel functional aspects of β-arrestins in regulating GPCR signaling have been discovered. These previously unanticipated roles of β-arrestins to act as signal transducers and mediators of G protein-independent signaling have led to the concept of biased agonism. Biased GPCR ligands are able to engage with their target receptors in a manner that preferentially activates only G protein- or β-arrestin-mediated downstream signaling. This offers the potential for next generation drugs with high selectivity to therapeutically relevant GPCR signaling pathways. In this review, we provide a summary of the recent studies highlighting G protein- or β-arrestin-biased GPCR signaling and the effects of biased ligands on disease pathogenesis and regulation.
AB - G protein-coupled receptors (GPCRs) are a family of cell-surface proteins that play critical roles in regulating a variety of pathophysiological processes and thus are targeted by almost a third of currently available therapeutics. It was originally thought that GPCRs convert extracellular stimuli into intracellular signals through activating G proteins, whereas β-arrestins have important roles in internalization and desensitization of the receptor. Over the past decade, several novel functional aspects of β-arrestins in regulating GPCR signaling have been discovered. These previously unanticipated roles of β-arrestins to act as signal transducers and mediators of G protein-independent signaling have led to the concept of biased agonism. Biased GPCR ligands are able to engage with their target receptors in a manner that preferentially activates only G protein- or β-arrestin-mediated downstream signaling. This offers the potential for next generation drugs with high selectivity to therapeutically relevant GPCR signaling pathways. In this review, we provide a summary of the recent studies highlighting G protein- or β-arrestin-biased GPCR signaling and the effects of biased ligands on disease pathogenesis and regulation.
KW - Biased signaling
KW - G protein
KW - G protein-coupled receptor
KW - β-arrestin
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U2 - 10.4062/biomolther.2016.165
DO - 10.4062/biomolther.2016.165
M3 - Article
VL - 25
SP - 12
EP - 25
JO - Biomolecules and Therapeutics
JF - Biomolecules and Therapeutics
SN - 1976-9148
IS - 1
ER -