Evidence map›Paper›PMID 34493720›Full record

ArticleNature communications2021

Proximity proteomics identifies PAK4 as a component of Afadin-Nectin junctions.

Yohendran Baskaran, Felicia Pei-Ling Tay, Elsa Yuen Wai Ng, Claire Lee Foon Swa, Sheena Wee, Jayantha Gunaratne, Edward Manser

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

14 citing papers in PubMed, 15 citations in OpenAlex.

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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

7 authors at 3 institutions in 1 country.

Yohendran Baskaran *sGSK Group, Institute of Molecular & Cell Biology, A*STAR, Singapore, Singapore.ORCID http://orcid.org/0000-0001-7021-3042
Felicia Pei-Ling Tay *FB Laboratory, Institute of Molecular & Cell Biology, A*STAR, Singapore, Singapore.
Elsa Yuen Wai NgsGSK Group, Institute of Molecular & Cell Biology, A*STAR, Singapore, Singapore.
Claire Lee Foon SwaQuantitative Proteomics Group, Institute of Molecular & Cell Biology, Singapore, Singapore.ORCID http://orcid.org/0000-0001-6099-130X
Sheena WeeQuantitative Proteomics Group, Institute of Molecular & Cell Biology, Singapore, Singapore.ORCID http://orcid.org/0000-0003-2536-3433
Jayantha GunaratneQuantitative Proteomics Group, Institute of Molecular & Cell Biology, Singapore, Singapore.
Edward MansersGSK Group, Institute of Molecular & Cell Biology, A*STAR, Singapore, Singapore. ed.manser@imb.a-star.edu.sg.ORCID http://orcid.org/0000-0002-7064-1191
Agency for Science, Technology and Research · SGInstitute of Molecular and Cell Biology · SGNational University of Singapore · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human PAK4 is an ubiquitously expressed p21-activated kinase which acts downstream of Cdc42. Since PAK4 is enriched in cell-cell junctions, we probed the local protein environment around the kinase with a view to understanding its location and substrates. We report that U2OS cells expressing PAK4-BirA-GFP identify a subset of 27 PAK4-proximal proteins that are primarily cell-cell junction components. Afadin/AF6 showed the highest relative biotin labelling and links to the nectin family of homophilic junctional proteins. Reciprocally >50% of the PAK4-proximal proteins were identified by Afadin BioID. Co-precipitation experiments failed to identify junctional proteins, emphasizing the advantage of the BioID method. Mechanistically PAK4 depended on Afadin for its junctional localization, which is similar to the situation in Drosophila. A highly ranked PAK4-proximal protein LZTS2 was immuno-localized with Afadin at cell-cell junctions. Though PAK4 and Cdc42 are junctional, BioID analysis did not yield conventional cadherins, indicating their spatial segregation. To identify cellular PAK4 substrates we then assessed rapid changes (12') in phospho-proteome after treatment with two PAK inhibitors. Among the PAK4-proximal junctional proteins seventeen PAK4 sites were identified. We anticipate mammalian group II PAKs are selective for the Afadin/nectin sub-compartment, with a demonstrably distinct localization from tight and cadherin junctions.

Indexed as

BiotinCarbon-Nitrogen Ligasescdc42 GTP-Binding ProteinCell Line, TumorEscherichia coli ProteinsGene Expression ProfilingGene Expression RegulationGreen Fluorescent ProteinsHumansIntercellular JunctionsIsotope LabelingMass SpectrometryMicrofilament ProteinsNectinsOsteoblastsp21-Activated KinasesafadinBiotinbirA protein, E coliCarbon-Nitrogen Ligasescdc42 GTP-Binding ProteinCDC42 protein, humanEscherichia coli ProteinsGreen Fluorescent ProteinsMicrofilament ProteinsNectinsp21-Activated KinasesPAK4 protein, humanProtein IsoformsRecombinant Fusion ProteinsRepressor Proteins

Identifiers

PMID34493720
PMCPMC8423818
OpenAlexW3198382191

What OpenQuestion holds

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LicenceCC BY
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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.