Evidence map›Paper›PMID 24441586›Full record

ArticleNature chemical biology2014

Integrated RAS signaling defined by parallel NMR detection of effectors and regulators.

Matthew J Smith, Mitsuhiko Ikura

Abstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

53 citing papers in PubMed, 93 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. The small GTPase MRAS is a broken switch.Nature communications · 2025
    Article
  5. Review
  6. Article
  7. Reconstitution and characterization of BRAF in complex with 14-3-3 and KRAS4B on nanodiscs.Protein science : a publication of the Protein Society · 2024
    Article
  8. Article
  9. Profiling Complex RAS-Effector Interactions Using NMR Spectroscopy.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  10. Article
  11. Allosteric site variants affect GTP hydrolysis on Ras.Protein science : a publication of the Protein Society · 2023
    Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

2 authors at 2 institutions in 1 country.

Matthew J SmithCampbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
Mitsuhiko Ikura1] Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada. [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
University Health Network · CAUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The RAS GTPase directs cell proliferation and survival by selectively relaying signals amid a dynamic network of regulatory enzymes and protein interactions. Oncogenic mutation of RAS alters cell growth by deleteriously controlling output to RAS-binding effectors. Mechanisms underlying multieffector interactions for both wild-type and oncogenic RAS are poorly understood owing to challenges in quantifying outputs to multiple pathways in parallel. Using highly selective NMR probes for wild-type and oncogenic (G12V) RAS, we develop a systematic approach that quantitatively measures RAS output in composite mixtures of GEF, GAP and effector RAS-binding domains (RBDs). We derive effector signaling hierarchies and establish how oscillating concentrations generate effector 'switching'. The G12V mutation highly perturbs this system, specifically altering interactions with RAL GTPase-specific GEFs and RAF kinases. We further reveal that RAS-RBD complexes show extensive feedback to full-length regulatory proteins. Our approach quantifies output from signaling hubs, here providing an integrated view of the RAS network.

Indexed as

Magnetic Resonance SpectroscopySignal TransductionAllosteric RegulationGTPase-Activating ProteinsHumansProtein Structure, TertiaryProto-Oncogene Proteins c-rafras ProteinsGTPase-Activating ProteinsProto-Oncogene Proteins c-rafras Proteins

Identifiers

PMID24441586
OpenAlexW2064086713

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.