Evidence map›Paper›PMID 36122391›Full record

ArticleJournal of the American Chemical Society2022

Fluorescent Biosensor for Measuring Ras Activity in Living Cells.

Ryan Weeks, Xin Zhou, Tina L Yuan, Jin Zhang

Open access · greenAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 18% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Sensing and Reprogramming Surface Receptor Activation With Synthetic Transcriptional Circuits.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Article
  5. Article
  6. Lysosomal PIPProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Surface-modified CMOS biosensors.Frontiers in bioengineering and biotechnology · 2024
    Review
  13. Review
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

4 authors at 2 institutions in 1 country.

Ryan WeeksDepartment of Pharmacology, University of California, San Diego, La Jolla, California 92093, United States.
Xin ZhouDepartment of Pharmacology, University of California, San Diego, La Jolla, California 92093, United States.ORCID 0000-0003-0734-0828
Tina L YuanNovartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, United States.
Jin ZhangDepartment of Pharmacology, University of California, San Diego, La Jolla, California 92093, United States.ORCID 0000-0001-7145-7823
University of California San Diego · USNovartis (United States) · US

Funding

Live-cell Activity Architecture in CancerR35CA197622 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jin Zhang · 2015 to 2026
$11.2M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
NCI NIH HHS R35 CA197622NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

The small GTPase Ras is a critical regulator of cell growth and proliferation. Its activity is frequently dysregulated in cancers, prompting decades of work to pharmacologically target Ras. Understanding Ras biology and developing effective Ras therapeutics both require probing Ras activity in its native context, yet tools to measure its activities in cellulo are limited. Here, we developed a ratiometric Ras activity reporter (RasAR) that provides quantitative measurement of Ras activity in living cells with high spatiotemporal resolution. We demonstrated that RasAR can probe live-cell activities of all the primary isoforms of Ras. Given that the functional roles of different isoforms of Ras are intimately linked to their subcellular distribution and regulation, we interrogated the spatiotemporal regulation of Ras utilizing subcellularly targeted RasAR and uncovered the role of Src kinase as an upstream regulator to inhibit HRas. Furthermore, we showed that RasAR enables capture of KRasG12C inhibition dynamics in living cells upon treatment with KRasG12C covalent inhibitors, including ARS1620, Sotorasib, and Adagrasib. We found in living cells a residual Ras activity lingers for hours in the presence of these inhibitors. Together, RasAR represents a powerful molecular tool to enable live-cell interrogation of Ras activity and facilitate the development of Ras inhibitors.

Indexed as

Biosensing TechniquesMonomeric GTP-Binding ProteinsAcetonitrilesPiperazinesProtein IsoformsPyrimidinessrc-Family KinasesAcetonitrilesadagrasibMonomeric GTP-Binding ProteinsPiperazinesProtein IsoformsPyrimidinessrc-Family Kinases

Identifiers

PMID36122391
PMCPMC10031818
OpenAlexW4296301826

What OpenQuestion holds

Textmetadata
LicenceTDM
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.