Evidence map›Paper›PMID 36865154›Full record

ArticlebioRxiv : the preprint server for biology2023

Atypical Chemokine Receptor 3 'Senses' CXC Chemokine Receptor 4 Activation Through GPCR Kinase Phosphorylation.

Christopher T Schafer, Qiuyan Chen, John J G Tesmer, Tracy M Handel

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, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Christopher T SchaferSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, USA.
Qiuyan ChenDepartments of Biological Sciences and of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, USA.
John J G TesmerDepartments of Biological Sciences and of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, USA.
Tracy M HandelSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, USA.
Purdue University West Lafayette · USUniversity of California San Diego · US

Funding

Structure, function, and inhibition of G protein-coupled receptor kinasesR01HL071818 · NHLBI · UNIVERSITY OF TEXAS AUSTIN · PI TESMER, JOHN · 2004 to 2023
$7.1M
It's a tug of war: structure, consequences, and inhibition of CXCR4 and ACKR3 responses to lymphocyte chemoattractant CXCL12R01AI161880 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HANDEL, TRACY M, KUFAREVA, IRINA · 2021 to 2025
$3.4M
Regulation of the metastasis promoting chemokine receptor ACKR3 by GPCR kinases, Gβγ and arrestinsR01CA254402 · NCI · PURDUE UNIVERSITY · PI HANDEL, TRACY M, TESMER, JOHN · 2020 to 2024
$3.2M
Insights into Activation Mechanisms of G Protein-Coupled and Atypical β-Arrestin-Coupled Chemokine ReceptorsR01GM133157 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI HANDEL, TRACY M, MILLAR, DAVID P · 2019 to 2022
$1.9M
GPCR - Linked RhoGEFs in Tumor Growth and MetastasisR01CA221289 · NCI · PURDUE UNIVERSITY · PI TESMER, JOHN · 2018 to 2022
$1.9M
Biased agonsim of CXCL12 stimulation of the atypical and classical receptors, ACKR3 and CXCR4F32GM137505 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SCHAFER, CHRISTOPHER T · 2020 to 2022
$163k
NCI NIH HHS R01 CA221289NCI NIH HHS R01 CA254402NHLBI NIH HHS R01 HL071818NIAID NIH HHS R01 AI161880NIGMS NIH HHS F32 GM137505NIGMS NIH HHS R01 GM133157
6 · The paper itself

Abstract

Atypical chemokine receptor 3 (ACKR3) is an arrestin-biased receptor that regulates extracellular chemokine levels through scavenging. The scavenging action mediates the availability of the chemokine CXCL12 for the G protein-coupled receptor (GPCR) CXCR4 and requires phosphorylation of the ACKR3 C-terminus by GPCR kinases (GRKs). ACKR3 is phosphorylated by GRK2 and GRK5, but the mechanisms by which these kinases regulate the receptor are unresolved. Here we mapped the phosphorylation patterns and determined that GRK5 phosphorylation of ACKR3 dominates β-arrestin recruitment and chemokine scavenging over GRK2. Co-activation of CXCR4 significantly enhanced phosphorylation by GRK2 through the liberation of Gβγ. These results suggest that ACKR3 'senses' CXCR4 activation through a GRK2-dependent crosstalk mechanism. Surprisingly, we also found that despite the requirement for phosphorylation, and the fact that most ligands promote β-arrestin recruitment, β-arrestins are dispensable for ACKR3 internalization and scavenging, suggesting a yet to be determined function for these adapter proteins.

Identifiers

PMID36865154
PMCPMC9980177
OpenAlexW4322207738

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.