Evidence map›Paper›PMID 24808183›Full record

ArticleThe Journal of biological chemistry2014

A chemical biology approach demonstrates G protein βγ subunits are sufficient to mediate directional neutrophil chemotaxis.

Chinmay R Surve, David Lehmann, Alan V Smrcka

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

31 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
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  6. Therapeutic inhibition of CXCR1/2: where do we stand?Internal and emergency medicine · 2023
    Review
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  11. Review
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  16. Surfen-mediated blockade of extratumoral chondroitin sulfate glycosaminoglycans inhibits glioblastoma invasion.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  17. Article
  18. Article
  19. Review
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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

3 authors at 2 institutions in 2 countries.

Chinmay R SurveFrom the Departments of Biochemistry and Biophysics and.
David LehmannPharmacology and Physiology, University of Rochester, Rochester, New York 14642.
Alan V SmrckaFrom the Departments of Biochemistry and Biophysics and Pharmacology and Physiology, University of Rochester, Rochester, New York 14642 alan_smrcka@urmc.rochester.edu.
University of Rochester · USInstitute of Molecular Biology and Biophysics · RU

Funding

The University of Rochester's Clinical and Translational Science InstituteUL1TR000042 · NCATS · UNIVERSITY OF ROCHESTER · PI BENNETT, NANCY M, KIEBURTZ, KARL D. · 2012 to 2015
$14.4M
Selective Targeting of G Protein beta gamma Subunits with Small MoleculesR01GM081772 · NIGMS · UNIVERSITY OF ROCHESTER · PI SMRCKA, ALAN V. · 2008 to 2017
$3.2M
NIGMS NIH HHS R01 GM081772NIGMS NIH HHS R01GM081772
6 · The paper itself

Abstract

Our laboratory has identified a number of small molecules that bind to G protein βγ subunits (Gβγ) by competing for peptide binding to the Gβγ "hot spot." M119/Gallein were identified as inhibitors of Gβγ subunit signaling. Here we examine the activity of another molecule identified in this screen, 12155, which we show that in contrast to M119/Gallein had no effect on Gβγ-mediated phospholipase C or phosphoinositide 3-kinase (PI3K) γ activation in vitro. Also in direct contrast to M119/Gallein, 12155 caused receptor-independent Ca(2+) release, and activated other downstream targets of Gβγ including extracellular signal regulated kinase (ERK), protein kinase B (Akt) in HL60 cells differentiated to neutrophils. We show that 12155 releases Gβγ in vitro from Gαi1β1γ2 heterotrimers by causing its dissociation from GαGDP without inducing nucleotide exchange in the Gα subunit. We used this novel probe to examine the hypothesis that Gβγ release is sufficient to direct chemotaxis of neutrophils in the absence of receptor or G protein α subunit activation. 12155 directed chemotaxis of HL60 cells and primary neutrophils in a transwell migration assay with responses similar to those seen for the natural chemotactic peptide n-formyl-Met-Leu-Phe. These data indicate that release of free Gβγ is sufficient to drive directional chemotaxis in a G protein-coupled receptor signaling-independent manner.

Indexed as

AnimalsCalciumChemotaxisCyclohexanesExtracellular Signal-Regulated MAP KinasesGTP-Binding Protein alpha Subunits, Gi-GoGTP-Binding Protein beta SubunitsGTP-Binding Protein gamma SubunitsHL-60 CellsHumansMiceNeutrophilsN-Formylmethionine Leucyl-PhenylalanineProto-Oncogene Proteins c-aktSignal TransductionXanthenesCalciumCyclohexanesExtracellular Signal-Regulated MAP KinasesgalleinGTP-Binding Protein alpha Subunits, Gi-GoGTP-Binding Protein beta SubunitsGTP-Binding Protein gamma SubunitsM119 compoundN-Formylmethionine Leucyl-PhenylalanineProto-Oncogene Proteins c-aktXanthenesCell SignalingChemical BiologyChemotaxisG ProteinG Protein-coupled Receptor (GPCR)

Identifiers

PMID24808183
PMCPMC4067212
OpenAlexW2054716361

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.