Evidence map›Paper›PMID 32965214›Full record

ArticleeLife2020

Light-regulated allosteric switch enables temporal and subcellular control of enzyme activity.

Mark Shaaya, Jordan Fauser, Anastasia Zhurikhina, Jason E Conage-Pough, Vincent Huyot, Martin Brennan, Cameron T Flower, Jacob Matsche, Shahzeb Khan, Viswanathan Natarajan and 5 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2020. 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
9.5field-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, 53 citations in OpenAlex.

  1. Article
  2. Article
  3. Directly adopting inverse biosensors to image live cell enzyme activities in nanodomains.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Multivalency Enables Signal Processing at Single Protein Level.Journal of the American Chemical Society · 2025
    Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Allosteric regulation of kinase activity in living cells.bioRxiv : the preprint server for biology · 2023
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Using Optogenetics to Model Cellular Effects of Alzheimer's Disease.International journal of molecular sciences · 2023
    Review
  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

15 authors at 5 institutions in 1 country.

Mark ShaayaDepartment of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, College of Medicine, Chicago, United States.ORCID https://orcid.org/0000-0003-4066-2693
Jordan FauserDepartment of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, College of Medicine, Chicago, United States.ORCID https://orcid.org/0000-0002-0675-8977
Anastasia ZhurikhinaWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, United States.
Jason E Conage-PoughThe David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States.ORCID http://orcid.org/0000-0002-1614-9374
Vincent HuyotDepartment of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, College of Medicine, Chicago, United States.
Martin BrennanDepartment of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, College of Medicine, Chicago, United States.
Cameron T FlowerThe David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States.ORCID http://orcid.org/0000-0002-9632-9913
Jacob MatscheDepartment of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, College of Medicine, Chicago, United States.
Shahzeb KhanDepartment of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, College of Medicine, Chicago, United States.
Viswanathan NatarajanDepartment of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, College of Medicine, Chicago, United States.
Jalees RehmanDepartment of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, College of Medicine, Chicago, United States.ORCID https://orcid.org/0000-0002-2787-9292
Pradeep KotaMarsico Lung Institute, Cystic Fibrosis Center and Department of Medicine, University of North Carolina, Chapel Hill, United States.
Forest M WhiteThe David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States.ORCID http://orcid.org/0000-0002-1545-1651
Denis TsygankovWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, United States.ORCID http://orcid.org/0000-0002-1180-3584
Andrei V KarginovDepartment of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, College of Medicine, Chicago, United States.ORCID https://orcid.org/0000-0003-2370-6383
University of Illinois Chicago · USPrecision for Medicine (United States) · USGeorgia Institute of Technology · USUniversity of Illinois Urbana-Champaign · USUniversity of North Carolina at Chapel Hill · US

Funding

TRPC6 Regulation of Lung Endothelial Barrier FunctionP01HL060678 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MALIK, ASRAR B. · 2000 to 2020
$40.1M
TRAINING PROGRAM IN LUNG BIOLOGY AND PATHOBIOLOGYT32HL007829 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DOLLY MEHTA · 1995 to 2026
$15.6M
Trans Network ProjectU54CA210180 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SARKARIA, JANN N., WHITE, FOREST M · 2016 to 2020
$10.2M
Graduate Training in Computational and Systems BiologyT32GM087237 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BURGE, CHRISTOPHER B · 2009 to 2023
$4.6M
Identification of adaptive response mechanisms in breast cancer by information theory and proteomicsU01CA238720 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KRAVCHENKO-BALASHA, NATALY, WHITE, FOREST M · 2019 to 2023
$2.0M
Src-mediated pathways regulating adherens junction assembly.R01GM118582 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KARGINOV, ANDREI V · 2017 to 2021
$1.8M
Engineered regulation of tyrosine phosphatase activity in living cellsR21CA212907 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KARGINOV, ANDREI V · 2017 to 2019
$683k
Optogenetic tools for the dissection of oncogenic signaling mediated by kinasesR21CA223915 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KARGINOV, ANDREI V, REHMAN, JALEES · 2018 to 2020
$580k
New methods for activation of kinases and kinase circuits in living cells.R21CA159179 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KARGINOV, ANDREI V · 2012 to 2013
$371k
Army Research Office W911NF-17-1-0395NCI NIH HHS R21 CA159179NCI NIH HHS R21 CA212907NCI NIH HHS R21 CA223915NCI NIH HHS U01 CA238720NCI NIH HHS U54 CA210180NHLBI NIH HHS P01 HL060678NHLBI NIH HHS T32 HL007829NIGMS NIH HHS R01 GM118582NIGMS NIH HHS T32 GM087237
6 · The paper itself

Abstract

Engineered allosteric regulation of protein activity provides significant advantages for the development of robust and broadly applicable tools. However, the application of allosteric switches in optogenetics has been scarce and suffers from critical limitations. Here, we report an optogenetic approach that utilizes an engineered Light-Regulated (LightR) allosteric switch module to achieve tight spatiotemporal control of enzymatic activity. Using the tyrosine kinase Src as a model, we demonstrate efficient regulation of the kinase and identify temporally distinct signaling responses ranging from seconds to minutes. LightR-Src off-kinetics can be tuned by modulating the LightR photoconversion cycle. A fast cycling variant enables the stimulation of transient pulses and local regulation of activity in a selected region of a cell. The design of the LightR module ensures broad applicability of the tool, as we demonstrate by achieving light-mediated regulation of Abl and bRaf kinases as well as Cre recombinase.

Indexed as

Allosteric RegulationEnzymesLightOptogeneticssrc-Family KinasesEnzymessrc-Family Kinasesallostericbiochemistrycell biologychemical biologyenzymenoneoptogeneticsprotein engineeringprotein kinaseSrc

Identifiers

PMID32965214
PMCPMC7577742
OpenAlexW3087941264

What OpenQuestion holds

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LicenceCC BY
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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.