Evidence map›Paper›PMID 24910098›Full record

ArticleMolecular cell2014

Directed network wiring identifies a key protein interaction in embryonic stem cell differentiation.

Norihisa Yasui, Greg M Findlay, Gerald D Gish, Marilyn S Hsiung, Jin Huang, Monika Tucholska, Lorne Taylor, Louis Smith, W Clifford Boldridge, Akiko Koide and 2 more

Abstract read
In one paragraph

Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
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

17 citing papers in PubMed.

  1. Article
  2. Binding mode-guided development of high-performance antibodies targeting site-specific posttranslational modifications.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Next-generation antibodies for post-translational modifications.Current opinion in structural biology · 2018
    Review
  10. Article
  11. Review
  12. Article
  13. Monobodies and other synthetic binding proteins for expanding protein science.Protein science : a publication of the Protein Society · 2017
    Review
  14. Article
  15. Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  16. Article
  17. Article
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.

Norihisa YasuiDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
Greg M FindlaySamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
Gerald D GishSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
Marilyn S HsiungSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
Jin HuangDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
Monika TucholskaSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
Lorne TaylorSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
Louis SmithDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
W Clifford BoldridgeDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
Akiko KoideDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
Tony PawsonSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Shohei KoideDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA. Electronic address: skoide@uchicago.edu.

Funding

Re-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2M
Foreign - Univ. of Toronto, PI-Dr. Sachdev SidhuU01GM094588 · NIGMS · UNIVERSITY OF CHICAGO · PI TAVERNA, SEAN D. · 2010 to 2014
$6.8M
Chaperone Assisted CrystallographyR01GM072688 · NIGMS · UNIVERSITY OF CHICAGO · PI KOSSIAKOFF, ANTHONY A · 2005 to 2012
$2.7M
Rational generation of directed protein-capture reagentsR01GM090324 · NIGMS · UNIVERSITY OF CHICAGO · PI KOIDE, SHOHEI · 2009 to 2013
$2.6M
High-performance affinity reagents for peptide epitopesR21CA132700 · NCI · UNIVERSITY OF CHICAGO · PI KOIDE, SHOHEI · 2008 to 2009
$367k
NCATS NIH HHS UL1 TR000430NCI NIH HHS R21 CA132700NCI NIH HHS R21-CA132700NIGMS NIH HHS R01 GM072688NIGMS NIH HHS R01-GM072688NIGMS NIH HHS R01 GM090324NIGMS NIH HHS R01-GM090324NIGMS NIH HHS U01 GM094588
6 · The paper itself

Abstract

Cell signaling depends on dynamic protein-protein interaction (PPI) networks, often assembled through modular domains each interacting with multiple peptide motifs. This complexity raises a conceptual challenge, namely to define whether a particular cellular response requires assembly of the complete PPI network of interest or can be driven by a specific interaction. To address this issue, we designed variants of the Grb2 SH2 domain ("pY-clamps") whose specificity is highly biased toward a single phosphotyrosine (pY) motif among many potential pYXNX Grb2-binding sites. Surprisingly, directing Grb2 predominantly to a single pY site of the Ptpn11/Shp2 phosphatase, but not other sites tested, was sufficient for differentiation of the essential primitive endoderm lineage from embryonic stem cells. Our data suggest that discrete connections within complex PPI networks can underpin regulation of particular biological events. We propose that this directed wiring approach will be of general utility in functionally annotating specific PPIs.

Indexed as

Cell DifferentiationAnimalsBinding SitesCell LineCrystallography, X-RayEmbryonic Stem CellsFibroblast Growth Factor 4GRB2 Adaptor ProteinMiceModels, MolecularProtein BindingProtein Interaction MapsProtein Structure, TertiaryProtein Tyrosine Phosphatase, Non-Receptor Type 11Signal TransductionFgf4 protein, mouseFibroblast Growth Factor 4GRB2 Adaptor ProteinGrb2 protein, mouseProtein Tyrosine Phosphatase, Non-Receptor Type 11Ptpn11 protein, mouse

Identifiers

PMID24910098
PMCPMC4090938

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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.