Evidence map›Paper›PMID 38273065›Full record

ArticleNature biotechnology2024

Computationally designed sensors detect endogenous Ras activity and signaling effectors at subcellular resolution.

Jason Z Zhang, William H Nguyen, Nathan Greenwood, John C Rose, Shao-En Ong, Dustin J Maly, David Baker

Open access · hybridAbstract read
In one paragraph

Article in Nature biotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
6.5field-weighted citation impact, top 2% 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

27 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Article
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  5. Sensing and Reprogramming Surface Receptor Activation With Synthetic Transcriptional Circuits.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  15. Beyond evolution:Biosafety and health · 2025
    Review
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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 4 institutions in 1 country.

Jason Z ZhangDepartment of Biochemistry, University of Washington, Seattle, WA, USA. jzz0428@uw.edu.ORCID http://orcid.org/0000-0003-0091-6273
William H NguyenDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0009-0003-6091-383X
Nathan GreenwoodDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
John C RoseDepartment of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1810-4337
Shao-En OngDepartment of Pharmacology, University of Washington, Seattle, WA, USA.
Dustin J Maly *Department of Biochemistry, University of Washington, Seattle, WA, USA. djmaly@uw.edu.ORCID http://orcid.org/0000-0003-0094-0177
David Baker *Department of Biochemistry, University of Washington, Seattle, WA, USA. dbaker@uw.edu.ORCID http://orcid.org/0000-0001-7896-6217
University of Washington · USCenter for Infectious Disease Research · USHoward Hughes Medical Institute · USStanford University · US

Funding

New Molecular Probes For Protein KinasesR01GM086858 · NIGMS · UNIVERSITY OF WASHINGTON · PI MALY, DUSTIN J · 2008 to 2025
$5.5M
Supplement to DEFINING PATHWAY-SPECIFIC KINASE SIGNALING MODULES WITH PROTEOMICSR01GM129090 · NIGMS · UNIVERSITY OF WASHINGTON · PI ONG, SHAO-EN · 2019 to 2022
$1.7M
Chemical Genetic Analysis of RAS SignalingR01GM145011 · NIGMS · UNIVERSITY OF WASHINGTON · PI MALY, DUSTIN J · 2022 to 2025
$1.5M
A NanoLC-Orbitrap Tribrid Instrument for Comprehensive Proteomics AnalysesS10OD021502 · OD · UNIVERSITY OF WASHINGTON · PI ONG, SHAO-EN · 2017 to 2017
$906k
NIGMS NIH HHS R01 GM086858NIGMS NIH HHS R01 GM129090NIGMS NIH HHS R01 GM145011NIH HHS S10 OD021502U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01GM086858U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01GM145011U.S. Department of Health & Human Services | National Institutes of Health (NIH) S10OD021502
6 · The paper itself

Abstract

The utility of genetically encoded biosensors for sensing the activity of signaling proteins has been hampered by a lack of strategies for matching sensor sensitivity to the physiological concentration range of the target. Here we used computational protein design to generate intracellular sensors of Ras activity (LOCKR-based Sensor for Ras activity (Ras-LOCKR-S)) and proximity labelers of the Ras signaling environment (LOCKR-based, Ras activity-dependent Proximity Labeler (Ras-LOCKR-PL)). These tools allow the detection of endogenous Ras activity and labeling of the surrounding environment at subcellular resolution. Using these sensors in human cancer cell lines, we identified Ras-interacting proteins in oncogenic EML4-Alk granules and found that Src-Associated in Mitosis 68-kDa (SAM68) protein specifically enhances Ras activity in the granules. The ability to subcellularly localize endogenous Ras activity should deepen our understanding of Ras function in health and disease and may suggest potential therapeutic strategies.

Indexed as

Biosensing Techniquesras ProteinsSignal TransductionAdaptor Proteins, Signal TransducingCell Line, TumorHumansAdaptor Proteins, Signal Transducingras Proteins

Identifiers

PMID38273065
PMCPMC11631767
OpenAlexW4391223677

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.