Evidence map›Paper›PMID 19620252›Full record

ArticleJournal of leukocyte biology2009

An arrestin-dependent multi-kinase signaling complex mediates MIP-1beta/CCL4 signaling and chemotaxis of primary human macrophages.

Ricky Cheung, Mobeen Malik, Vipa Ravyn, Brian Tomkowicz, Andrzej Ptasznik, Ronald G Collman

Open access · bronzeAbstract read
In one paragraph

Article in Journal of leukocyte biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Cardiomyocyte β-arrestins mediate inflammation and cGAS-STING activation in CVB3 viral myocarditis.American journal of physiology. Heart and circulatory physiology · 2026
    Article
  5. GPCR Biased Signaling in Cancer.Handbook of experimental pharmacology · 2026
    Review
  6. Neutrophil diversity and function in health and disease.Signal transduction and targeted therapy · 2024
    Review
  7. Arrestins: A Small Family of Multi-Functional Proteins.International journal of molecular sciences · 2024
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Review
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

6 authors at 2 institutions in 1 country.

Ricky CheungPulmonary, Allergy and Critical Care, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6061, USA.
Mobeen Malik
Vipa Ravyn
Brian Tomkowicz
Andrzej Ptasznik
Ronald G Collman
University of Pennsylvania Health System · USUniversity of Pennsylvania · US

Funding

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ROBERT GROSS · 1999 to 2026
$78.6M
SCID HU MODEL FOR HIV INFECTION OF THE CNSP01NS027405 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI GONZALEZ-SCARANO, FRANCISCO · 1989 to 2007
$8.2M
HIV: gp120, Chemokine Receptors &Macrophage ActivationR01MH061139 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI COLLMAN, RONALD G · 1999 to 2015
$5.2M
Molecular and Cellular Biology of HIV EncephalopathyP50NS027405 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI GONZALEZ-SCARANO, FRANCISCO · 2008 to 2009
$2.2M
Crosstalk between oncoprotein and chemokine signalingR01CA108552 · NCI · UNIVERSITY OF PENNSYLVANIA · PI PTASZNIK, ANDRZEJ · 2005 to 2007
$698k
NCI NIH HHS CA108552NIAID NIH HHS P30 AI045008NIMH NIH HHS MH061139NINDS NIH HHS NS027405
6 · The paper itself

Abstract

MIP-1beta/CCL4 is a principal regulator of macrophage migration and signals through CCR5. Several protein kinases are linked to CCR5 in macrophages including the src kinase Lyn, PI3K, focal adhesion related kinase Pyk2, and members of the MAPK family, but whether and how these kinases regulate macrophage chemotaxis are not known. To define the role of these signaling molecules, we examined the functions and interactions of endogenous proteins in primary human macrophages. Using siRNA gene silencing and pharmacologic inhibition, we show that chemotaxis in response to CCR5 stimulation by MIP-1beta requires activation of Pyk2, PI3K p85, and Lyn, as well as MAPK ERK. MIP-1beta activation of CCR5 triggered translocation of Pyk2 and PI3K p85 from the cytoplasm to colocalize with Lyn at the plasma membrane with formation of a multimolecular complex. We show further that arrestins were recruited into the complex, and arrestin down-regulation impaired complex formation and macrophage chemotaxis toward MIP-1beta. Together, these results identify a novel mechanism of chemokine receptor regulation of chemotaxis and suggest that arrestins may serve as scaffolding proteins linking CCR5 to multiple downstream signaling molecules in a biologically important primary human cell type.

Indexed as

ArrestinCell MembraneChemokine CCL4ChemotaxisCytoplasmFocal Adhesion Kinase 2HumansMacrophagesMultienzyme ComplexesPhosphatidylinositol 3-KinasesProtein TransportReceptors, CCR5Signal Transductionsrc-Family KinasesArrestinCCL4 protein, humanChemokine CCL4Focal Adhesion Kinase 2lyn protein-tyrosine kinaseMultienzyme ComplexesPhosphatidylinositol 3-KinasesPTK2B protein, humanReceptors, CCR5src-Family Kinases

Identifiers

PMID19620252
PMCPMC2752020
OpenAlexW2125365369

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.