Evidence map›Paper›PMID 27331810›Full record

ArticleInternational journal of molecular sciences2016

New Insights into Mechanisms and Functions of Chemokine (C-X-C Motif) Receptor 4 Heteromerization in Vascular Smooth Muscle.

Ann E Evans, Abhishek Tripathi, Heather M LaPorte, Lioubov I Brueggemann, Abhay Kumar Singh, Lauren J Albee, Kenneth L Byron, Nadya I Tarasova, Brian F Volkman, Thomas Yoonsang Cho and 2 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.0field-weighted citation impact, top 12% of its field
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

27 citing papers in PubMed, 33 citations in OpenAlex.

  1. Activation of Chemokine (C-C Motif) Receptor 1 Modulates αJournal of the American Heart Association · 2025
    Article
  2. Review
  3. Article
  4. Article
  5. αPharmacological research · 2023
    Article
  6. αProceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  7. Review
  8. Cardioprotective Potential of Exogenous Ubiquitin.Cardiovascular drugs and therapy · 2021
    Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 1 country.

Ann E EvansBurn and Shock Trauma Research Institute, Department of Surgery, Loyola University Chicago Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA. anevans@lumc.edu.
Abhishek TripathiBurn and Shock Trauma Research Institute, Department of Surgery, Loyola University Chicago Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA. omnamahshiva80@gmail.com.
Heather M LaPorteBurn and Shock Trauma Research Institute, Department of Surgery, Loyola University Chicago Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA. hlaporte@luc.edu.
Lioubov I BrueggemannDepartment of Molecular Pharmacology and Therapeutics, Loyola University Chicago Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA. lbruegg@luc.edu.
Abhay Kumar SinghEdward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1100 South Grand Blvd., St. Louis, MO 63104, USA. singh@slu.edu.
Lauren J AlbeeBurn and Shock Trauma Research Institute, Department of Surgery, Loyola University Chicago Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA. lalbee@luc.edu.
Kenneth L ByronEdward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1100 South Grand Blvd., St. Louis, MO 63104, USA. kbyron@luc.edu.
Nadya I TarasovaCancer and Inflammation Program, National Cancer Institute, PO Box B, Frederick, MD 21702-1201, USA. tarasovn@mail.nih.gov.
Brian F VolkmanDepartment of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. bvolkman@gmail.com.
Thomas Yoonsang ChoEdward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1100 South Grand Blvd., St. Louis, MO 63104, USA. ycho9@slu.edu.
Vadim GaponenkoDepartment of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 900 S Ashland, Chicago, IL 60607, USA. vadimg@uic.edu.
Matthias MajetschakBurn and Shock Trauma Research Institute, Department of Surgery, Loyola University Chicago Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA. mmajetschak@luc.edu.
Loyola University Chicago · USSaint Louis University · USMedical College of Wisconsin · USNational Cancer Institute · USUniversity of Illinois Chicago · US

Funding

Structural Basis for Chemokine FunctionR01AI058072 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI VOLKMAN, BRIAN F · 2004 to 2019
$4.1M
TRAINING IN TRAUMA AND BURN RESEARCHT32GM008750 · NIGMS · LOYOLA UNIVERSITY CHICAGO · PI CHOUDHRY, MASHKOOR A, GONZALEZ, RICHARD PAUL · 2000 to 2023
$2.9M
Structural Basis for Chemokine FunctionR37AI058072 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI Brian F Volkman · 2020 to 2026
$2.8M
Self-assembling protoviral nanoparticlesZIABC011307 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TARASOVA, NADYA · 2010 to 2022
$2.7M
Regulation of tyrosine kinase signaling through interaction with membrane lipidsR01CA188427 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI GAPONENKO, VADIM V, TYNER, ANGELA L · 2015 to 2019
$2.1M
Design of Therapeutic Peptide-Based NanoparticlesR01CA135341 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI GAPONENKO, VADIM V · 2010 to 2014
$1.5M
Chemokine control of cardiovascular function during hemorrhagic shockR01GM107495 · NIGMS · UNIVERSITY OF SOUTH FLORIDA · PI MAJETSCHAK, MATTHIAS · 2014 to 2017
$1.1M
Therapeutic Application of Small Molecule MIF Inhibitors in Rheumatoid ArthritisK01AR060300 · NIAMS · YALE UNIVERSITY · PI CHO, THOMAS YOONSANG · 2011 to 2015
$628k
Peptide-based nanoparticle inhibition of CCR3-mediated inflammatory cell recruitmR21HL118588 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI GAPONENKO, VADIM V · 2013 to 2014
$423k
NCI NIH HHS R01 CA135341NCI NIH HHS R01 CA188427NHLBI NIH HHS R21 HL118588NIAID NIH HHS R01 AI058072NIAID NIH HHS R37 AI058072NIAMS NIH HHS K01 AR060300NIGMS NIH HHS R01 GM107495NIGMS NIH HHS T32 GM008750
6 · The paper itself

Abstract

Recent evidence suggests that C-X-C chemokine receptor type 4 (CXCR4) heteromerizes with α1A/B-adrenoceptors (AR) and atypical chemokine receptor 3 (ACKR3) and that CXCR4:α1A/B-AR heteromers are important for α₁-AR function in vascular smooth muscle cells (VSMC). Structural determinants for CXCR4 heteromerization and functional consequences of CXCR4:α1A/B-AR heteromerization in intact arteries, however, remain unknown. Utilizing proximity ligation assays (PLA) to visualize receptor interactions in VSMC, we show that peptide analogs of transmembrane-domain (TM) 2 and TM4 of CXCR4 selectively reduce PLA signals for CXCR4:α1A-AR and CXCR4:ACKR3 interactions, respectively. While both peptides inhibit CXCL12-induced chemotaxis, only the TM2 peptide inhibits phenylephrine-induced Ca(2+)-fluxes, contraction of VSMC and reduces efficacy of phenylephrine to constrict isolated arteries. In a Cre-loxP mouse model to delete CXCR4 in VSMC, we observed 60% knockdown of CXCR4. PLA signals for CXCR4:α1A/B-AR and CXCR4:ACKR3 interactions in VSMC, however, remained constant. Our observations point towards TM2/4 of CXCR4 as possible contact sites for heteromerization and suggest that TM-derived peptide analogs permit selective targeting of CXCR4 heteromers. A molecular dynamics simulation of a receptor complex in which the CXCR4 homodimer interacts with α1A-AR via TM2 and with ACKR3 via TM4 is presented. Our findings further imply that CXCR4:α1A-AR heteromers are important for intrinsic α₁-AR function in intact arteries and provide initial and unexpected insights into the regulation of CXCR4 heteromerization in VSMC.

Indexed as

Protein MultimerizationAnimalsBinding SitesCalciumCell LineCells, CulturedFemaleHumansMaleMiceMolecular Dynamics SimulationMuscle, Smooth, VascularProtein BindingRatsRats, Sprague-DawleyReceptors, Adrenergic, alpha-1CalciumCmkor1 protein, mouseReceptors, Adrenergic, alpha-1Receptors, CXCRReceptors, CXCR4adrenergic receptoratypical chemokine receptor 3blood pressure(C-X-C motif) receptor 7G protein-coupled receptorreceptor heteromerstructural modelingvascular function

Identifiers

PMID27331810
PMCPMC4926503
OpenAlexW2441432649

What OpenQuestion holds

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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.