Evidence map›Paper›PMID 23839946›Full record

ArticleThe Journal of biological chemistry2013

Intrinsic selectivity of Notch 1 for Delta-like 4 over Delta-like 1.

Marie Blanke Andrawes, Xiang Xu, Hong Liu, Scott B Ficarro, Jarrod A Marto, Jon C Aster, Stephen C Blacklow

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing 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

74 citing papers in PubMed, 129 citations in OpenAlex.

  1. Article
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  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Biomolecules · 2022
    Article
  13. Article
  14. mBio · 2022
    Article
  15. Significant Roles of NotchMolecules (Basel, Switzerland) · 2022
    Review
  16. Signalling dynamics in embryonic development.The Biochemical journal · 2021
    Review
  17. Article
  18. Review
  19. Biophysics of Notch Signaling.Annual review of biophysics · 2021
    Review
  20. Current Views on the Roles ofBiomolecules · 2021
    Review

14 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

7 authors at 2 institutions in 1 country.

Marie Blanke AndrawesFrom the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115,; the Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, and.
Xiang XuFrom the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115,; the Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, and.
Hong Liuthe Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, and.
Scott B FicarroFrom the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115,; the Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, and.
Jarrod A MartoFrom the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115,; the Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, and.
Jon C Asterthe Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02114.
Stephen C BlacklowFrom the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115,; the Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, and. Electronic address: Stephen_blacklow@hms.harvard.edu.
Dana-Farber Cancer Institute · USHarvard University · US

Funding

Protein CoreP01CA119070 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ASTER, JON C. · 2006 to 2016
$10.3M
Structure and Function in Notch SignalingR01CA092433 · NCI · HARVARD MEDICAL SCHOOL · PI BLACKLOW, STEPHEN C. · 2002 to 2016
$5.0M
NCI NIH HHS P01 CA119070NCI NIH HHS R01 CA092433
6 · The paper itself

Abstract

Notch signaling makes critical contributions to cell fate determination in all metazoan organisms, yet remarkably little is known about the binding affinity of the four mammalian Notch receptors for their three Delta-like and two Jagged family ligands. Here, we utilized signaling assays and biochemical studies of purified recombinant ligand and receptor molecules to investigate the differences in signaling behavior and intrinsic affinity between Notch1-Dll1 and Notch1-Dll4 complexes. Systematic deletion mutagenesis of the human Notch1 ectodomain revealed that epidermal growth factor (EGF) repeats 6-15 are sufficient to maintain signaling in a reporter assay at levels comparable with the full-length receptor, and identified important contributions from EGF repeats 8-10 in conveying an activating signal in response to either Dll1 or Dll4. Truncation studies of the Dll1 and Dll4 ectodomains showed that the MNNL-EGF3 region was both necessary and sufficient for full activation. Plate-based and cell binding assays revealed a specific, calcium-dependent interaction between cell-surface and recombinant Notch receptors and ligand molecules. Finally, direct measurement of the binding affinity of Notch1 EGF repeats 6-15 for Dll1 and Dll4 revealed that Dll4 binds with at least an order of magnitude higher affinity than Dll1. Together, these studies give new insights into the features of ligand recognition by Notch1, and highlight how intrinsic differences in the biochemical behavior of receptor-ligand complexes can influence receptor-mediated responses of developmental signaling pathways.

Indexed as

Adaptor Proteins, Signal TransducingAmino Acid SequenceCalcium-Binding ProteinsHEK293 CellsHumansIntercellular Signaling Peptides and ProteinsMembrane ProteinsProtein BindingProtein Structure, TertiaryReceptor, Notch1Repetitive Sequences, Amino AcidSequence DeletionSignal TransductionAdaptor Proteins, Signal TransducingCalcium-Binding ProteinsDLK1 protein, humanDLL4 protein, humanIntercellular Signaling Peptides and ProteinsMembrane ProteinsNOTCH1 protein, humanReceptor, Notch1Biolayer InterferometryCell-Cell InteractionCell SignalingCell Surface ReceptorNotch PathwayReceptor-Ligand InteractionReceptor Structure-FunctionRecombinant Protein Expression

Identifiers

PMID23839946
PMCPMC3757209
OpenAlexW2052306889

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.