Evidence map›Paper›PMID 14737186›Full record

ArticlePLoS biology2004

HIV-1 Nef binds the DOCK2-ELMO1 complex to activate rac and inhibit lymphocyte chemotaxis.

Ajit Janardhan, Tomek Swigut, Brian Hill, Michael P Myers, Jacek Skowronski

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

62 citing papers in PubMed, 121 citations in OpenAlex.

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2 more citing papers are in PubMed but not listed here.

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

5 authors at 2 institutions in 1 country.

Ajit JanardhanCold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
Tomek Swigut
Brian Hill
Michael P Myers
Jacek Skowronski
Stony Brook University · USCold Spring Harbor Laboratory · US

Funding

MOLECULAR INTERACTIONS OF NEF AND AIDS PATHOGENESISR01AI042561 · NIAID · COLD SPRING HARBOR LABORATORY · PI SKOWRONSKI, JACEK · 1998 to 2007
$4.7M
NIAID NIH HHS AI-42561NIAID NIH HHS R01 AI042561
6 · The paper itself

Abstract

The infectious cycle of primate lentiviruses is intimately linked to interactions between cells of the immune system. Nef, a potent virulence factor, alters cellular environments to increase lentiviral replication in the host, yet the mechanisms underlying these effects have remained elusive. Since Nef likely functions as an adaptor protein, we exploited a proteomic approach to directly identify molecules that Nef targets to subvert the signaling machinery in T cells. We purified to near homogeneity a major Nef-associated protein complex from T cells and identified by mass spectroscopy its subunits as DOCK2-ELMO1, a key activator of Rac in antigen- and chemokine-initiated signaling pathways, and Rac. We show that Nef activates Rac in T cell lines and in primary T cells following infection with HIV-1 in the absence of antigenic stimuli. Nef activates Rac by binding the DOCK2-ELMO1 complex, and this interaction is linked to the abilities of Nef to inhibit chemotaxis and promote T cell activation. Our data indicate that Nef targets a critical switch that regulates Rac GTPases downstream of chemokine- and antigen-initiated signaling pathways. This interaction enables Nef to influence multiple aspects of T cell function and thus provides an important mechanism by which Nef impacts pathogenesis by primate lentiviruses.

Indexed as

Adaptor Proteins, Signal TransducingCD28 AntigensCD3 ComplexCell MovementChemotaxisEpitopesGene Products, nefGTPase-Activating ProteinsGuanine Nucleotide Exchange FactorsHIV-1HumansInterleukin-2Jurkat CellsLentivirusLymphocytesMass SpectrometryAdaptor Proteins, Signal TransducingCD28 AntigensCD3 ComplexDOCK2 protein, humanELMO1 protein, humanEpitopesGene Products, nefGTPase-Activating ProteinsGuanine Nucleotide Exchange FactorsInterleukin-2nef Gene Products, Human Immunodeficiency Virusrac1 GTP-Binding ProteinRAC2 GTP-Binding Proteinrac GTP-Binding Proteins

Identifiers

PMID14737186
PMCPMC314466
OpenAlexW2147108500

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.