In vivo brain GPCR signaling elucidated by phosphoproteomics

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Standard

In vivo brain GPCR signaling elucidated by phosphoproteomics. / Liu, Jeffrey J; Sharma, Kirti; Zangrandi, Luca; Chen, Chongguang; Humphrey, Sean J; Chiu, Yi-Ting; Spetea, Mariana; Liu-Chen, Lee-Yuan; Schwarzer, Christoph; Mann, Matthias.

In: Science (New York, N.Y.), Vol. 360, No. 6395, 2018, p. 1-11.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Liu, JJ, Sharma, K, Zangrandi, L, Chen, C, Humphrey, SJ, Chiu, Y-T, Spetea, M, Liu-Chen, L-Y, Schwarzer, C & Mann, M 2018, 'In vivo brain GPCR signaling elucidated by phosphoproteomics', Science (New York, N.Y.), vol. 360, no. 6395, pp. 1-11. https://doi.org/10.1126/science.aao4927

APA

Liu, J. J., Sharma, K., Zangrandi, L., Chen, C., Humphrey, S. J., Chiu, Y-T., Spetea, M., Liu-Chen, L-Y., Schwarzer, C., & Mann, M. (2018). In vivo brain GPCR signaling elucidated by phosphoproteomics. Science (New York, N.Y.), 360(6395), 1-11. https://doi.org/10.1126/science.aao4927

Vancouver

Liu JJ, Sharma K, Zangrandi L, Chen C, Humphrey SJ, Chiu Y-T et al. In vivo brain GPCR signaling elucidated by phosphoproteomics. Science (New York, N.Y.). 2018;360(6395):1-11. https://doi.org/10.1126/science.aao4927

Author

Liu, Jeffrey J ; Sharma, Kirti ; Zangrandi, Luca ; Chen, Chongguang ; Humphrey, Sean J ; Chiu, Yi-Ting ; Spetea, Mariana ; Liu-Chen, Lee-Yuan ; Schwarzer, Christoph ; Mann, Matthias. / In vivo brain GPCR signaling elucidated by phosphoproteomics. In: Science (New York, N.Y.). 2018 ; Vol. 360, No. 6395. pp. 1-11.

Bibtex

@article{8f7aa40ef4c34c91a5c2c4de95dbdc91,
title = "In vivo brain GPCR signaling elucidated by phosphoproteomics",
abstract = "A systems view of G protein-coupled receptor (GPCR) signaling in its native environment is central to the development of GPCR therapeutics with fewer side effects. Using the kappa opioid receptor (KOR) as a model, we employed high-throughput phosphoproteomics to investigate signaling induced by structurally diverse agonists in five mouse brain regions. Quantification of 50,000 different phosphosites provided a systems view of KOR in vivo signaling, revealing novel mechanisms of drug action. Thus, we discovered enrichment of the mechanistic target of rapamycin (mTOR) pathway by U-50,488H, an agonist causing aversion, which is a typical KOR-mediated side effect. Consequently, mTOR inhibition during KOR activation abolished aversion while preserving beneficial antinociceptive and anticonvulsant effects. Our results establish high-throughput phosphoproteomics as a general strategy to investigate GPCR in vivo signaling, enabling prediction and modulation of behavioral outcomes.",
author = "Liu, {Jeffrey J} and Kirti Sharma and Luca Zangrandi and Chongguang Chen and Humphrey, {Sean J} and Yi-Ting Chiu and Mariana Spetea and Lee-Yuan Liu-Chen and Christoph Schwarzer and Matthias Mann",
note = "Copyright {\textcopyright} 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",
year = "2018",
doi = "10.1126/science.aao4927",
language = "English",
volume = "360",
pages = "1--11",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6395",

}

RIS

TY - JOUR

T1 - In vivo brain GPCR signaling elucidated by phosphoproteomics

AU - Liu, Jeffrey J

AU - Sharma, Kirti

AU - Zangrandi, Luca

AU - Chen, Chongguang

AU - Humphrey, Sean J

AU - Chiu, Yi-Ting

AU - Spetea, Mariana

AU - Liu-Chen, Lee-Yuan

AU - Schwarzer, Christoph

AU - Mann, Matthias

N1 - Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

PY - 2018

Y1 - 2018

N2 - A systems view of G protein-coupled receptor (GPCR) signaling in its native environment is central to the development of GPCR therapeutics with fewer side effects. Using the kappa opioid receptor (KOR) as a model, we employed high-throughput phosphoproteomics to investigate signaling induced by structurally diverse agonists in five mouse brain regions. Quantification of 50,000 different phosphosites provided a systems view of KOR in vivo signaling, revealing novel mechanisms of drug action. Thus, we discovered enrichment of the mechanistic target of rapamycin (mTOR) pathway by U-50,488H, an agonist causing aversion, which is a typical KOR-mediated side effect. Consequently, mTOR inhibition during KOR activation abolished aversion while preserving beneficial antinociceptive and anticonvulsant effects. Our results establish high-throughput phosphoproteomics as a general strategy to investigate GPCR in vivo signaling, enabling prediction and modulation of behavioral outcomes.

AB - A systems view of G protein-coupled receptor (GPCR) signaling in its native environment is central to the development of GPCR therapeutics with fewer side effects. Using the kappa opioid receptor (KOR) as a model, we employed high-throughput phosphoproteomics to investigate signaling induced by structurally diverse agonists in five mouse brain regions. Quantification of 50,000 different phosphosites provided a systems view of KOR in vivo signaling, revealing novel mechanisms of drug action. Thus, we discovered enrichment of the mechanistic target of rapamycin (mTOR) pathway by U-50,488H, an agonist causing aversion, which is a typical KOR-mediated side effect. Consequently, mTOR inhibition during KOR activation abolished aversion while preserving beneficial antinociceptive and anticonvulsant effects. Our results establish high-throughput phosphoproteomics as a general strategy to investigate GPCR in vivo signaling, enabling prediction and modulation of behavioral outcomes.

U2 - 10.1126/science.aao4927

DO - 10.1126/science.aao4927

M3 - Journal article

C2 - 29930108

VL - 360

SP - 1

EP - 11

JO - Science

JF - Science

SN - 0036-8075

IS - 6395

ER -

ID: 198717121