Evidence map›Paper›PMID 36993369›Full record

ArticlebioRxiv : the preprint server for biology2023

Phosphorylation barcodes direct biased chemokine signaling at CXCR3.

Dylan S Eiger, Jeffrey S Smith, Tujin Shi, Tomasz Maciej Stepniewski, Chia-Feng Tsai, Christopher Honeycutt, Noelia Boldizsar, Julia Gardner, Carrie D Nicora, Ahmed M Moghieb and 13 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 7 institutions in 3 countries.

Dylan S EigerDepartment of Biochemistry, Duke University, Durham, NC, 27710, USA.
Jeffrey S SmithDepartment of Dermatology, Massachusetts General Hospital, Boston, MA, 02114, USA.
Tujin ShiBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.
Tomasz Maciej StepniewskiResearch Programme on Biomedical Informatics (GRIB), Department of Experimental and Health Sciences of Pompeu Fabra University (UPF)-Hospital del Mar Medical Research Institute (IMIM), Barcelona, 08003, Spain.
Chia-Feng TsaiBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.
Christopher HoneycuttTrinity College, Duke University, Durham, NC, 27710, USA.
Noelia BoldizsarTrinity College, Duke University, Durham, NC, 27710, USA.
Julia GardnerTrinity College, Duke University, Durham, NC, 27710, USA.
Carrie D NicoraBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.
Ahmed M MoghiebR&D Research, GlaxoSmithKline, Collegeville, PA, 19426, USA.
Kouki KawakamiDepartment of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8577, Japan.
Issac ChoiDepartment of Medicine, Duke University, Durham, NC 27710 USA.
Kevin ZhengTrinity College, Duke University, Durham, NC, 27710, USA.
Anmol WarmanTrinity College, Duke University, Durham, NC, 27710, USA.
Priya AlagesanDepartment of Biochemistry, Duke University, Durham, NC, 27710, USA.
Nicole M KnapeDepartment of Biochemistry, Duke University, Durham, NC, 27710, USA.
Ouwen HuangDepartment of Biomedical Engineering, Duke University, Durham, NC, 27710, USA.
Justin D SilvermanCollege of Information Sciences and Technology, The Pennsylvania State University, University Park, PA, 16802, USA.
Richard D SmithBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.
Asuka InoueDepartment of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8577, Japan.
Jana SelentResearch Programme on Biomedical Informatics (GRIB), Department of Experimental and Health Sciences of Pompeu Fabra University (UPF)-Hospital del Mar Medical Research Institute (IMIM), Barcelona, 08003, Spain.
Jon M JacobsBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.
Sudarshan RajagopalDepartment of Biochemistry, Duke University, Durham, NC, 27710, USA.
Duke University · USPacific Northwest National Laboratory · USTohoku University · JPUniversitat Pompeu Fabra · ESBrigham and Women's Hospital · USGlaxoSmithKline (United States) · USPennsylvania State University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007171 · NIGMS · DUKE UNIVERSITY · PI KONTOS, CHRISTOPHER D · 1985 to 2021
$31.2M
Equipment Supplement Request for a Research Resource for Ultra-sensitive High Throughput ProteomicsP41GM103493 · NIGMS · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI KELLY, RYAN T · 2012 to 2022
$22.6M
Biasing CXCR3 Signaling to Modulate the Inflammatory ResponseR01GM122798 · NIGMS · DUKE UNIVERSITY · PI RAJAGOPAL, SUDARSHAN · 2017 to 2025
$3.2M
Targeted proteomics technology for accurate quantitative single-cell proteomicsR01GM139858 · NIGMS · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI SHI, TUJIN · 2021 to 2024
$1.6M
Noncanonical Receptor Signaling in Pulmonary Arterial HypertensionK08HL114643 · NHLBI · DUKE UNIVERSITY · PI RAJAGOPAL, SUDARSHAN K · 2013 to 2017
$607k
American Heart Association-American Stroke Association 20PRE35120592NHLBI NIH HHS K08 HL114643NIGMS NIH HHS P41 GM103493NIGMS NIH HHS R01 GM122798NIGMS NIH HHS R01 GM139858NIGMS NIH HHS T32 GM007171
6 · The paper itself

Abstract

G protein-coupled receptor (GPCR) biased agonism, the activation of some signaling pathways over others, is thought to largely be due to differential receptor phosphorylation, or "phosphorylation barcodes." At chemokine receptors, ligands act as "biased agonists" with complex signaling profiles, which contributes to the limited success in pharmacologically targeting these receptors. Here, mass spectrometry-based global phosphoproteomics revealed that CXCR3 chemokines generate different phosphorylation barcodes associated with differential transducer activation. Chemokine stimulation resulted in distinct changes throughout the kinome in global phosphoproteomic studies. Mutation of CXCR3 phosphosites altered β-arrestin conformation in cellular assays and was confirmed by molecular dynamics simulations. T cells expressing phosphorylation-deficient CXCR3 mutants resulted in agonist- and receptor-specific chemotactic profiles. Our results demonstrate that CXCR3 chemokines are non-redundant and act as biased agonists through differential encoding of phosphorylation barcodes and lead to distinct physiological processes.

Indexed as

beta-arrestinbiased agonismchemokinechemotaxisCXCR3G protein-coupled receptorMAP kinasemass spectrometrymolecular dynamicsphosphoproteomics

Identifiers

PMID36993369
PMCPMC10055163
OpenAlexW4324378456

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.