Evidence map›Paper›PMID 28288122›Full record

ArticleNature methods2017

Genetically encoded biosensors for visualizing live-cell biochemical activity at super-resolution.

Gary C H Mo, Brian Ross, Fabian Hertel, Premashis Manna, Xinxing Yang, Eric Greenwald, Chris Booth, Ashlee M Plummer, Brian Tenner, Zan Chen and 9 more

Open access · greenAbstract read
In one paragraph

Article in Nature methods, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
26.1field-weighted citation impact, top 1% 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

80 citing papers in PubMed, 169 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. 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
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Electrochemically controlled switching of dyes for enhanced superresolution optical fluctuation imaging (EC-SOFI).Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. GPCR signaling via cAMP nanodomains.The Biochemical journal · 2025
    Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. The focal adhesion protein talin is a mechanically gated A-kinase anchoring protein.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article

20 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

19 authors at 6 institutions in 2 countries.

Gary C H MoDepartment of Pharmacology, University of California San Diego, La Jolla, California, USA.
Brian RossDepartment of Pharmacology, University of California San Diego, La Jolla, California, USA.
Fabian HertelDepartment of Pharmacology, University of California San Diego, La Jolla, California, USA.
Premashis MannaJILA, University of Colorado and NIST, Boulder, Colorado, USA.
Xinxing YangDepartment of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Eric GreenwaldDepartment of Pharmacology, University of California San Diego, La Jolla, California, USA.
Chris BoothDepartment of Pharmacology, University of California San Diego, La Jolla, California, USA.
Ashlee M PlummerT. C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland, USA.
Brian TennerDepartment of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Zan ChenDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Yuxiao WangDepartment of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia, USA.
Eileen J KennedyDepartment of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia, USA.
Philip A ColeDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Karen G FlemingT. C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland, USA.
Amy PalmerDepartment of Chemistry and Biochemistry, University of Colorado, Boulder, Boulder, Colorado, USA.
Ralph JimenezJILA, University of Colorado and NIST, Boulder, Colorado, USA.ORCID http://orcid.org/0000-0002-8989-405X
Jie XiaoDepartment of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Peter DedeckerDepartment of Chemistry, KU Leuven, Heverlee, Belgium.
Jin ZhangDepartment of Pharmacology, University of California San Diego, La Jolla, California, USA.
Johns Hopkins University · USUniversity of California San Diego · USJoint Institute for Laboratory Astrophysics · USUniversity of Georgia · USKU Leuven · BEUniversity of Colorado Boulder · US

Funding

PROGRAM IN MOLECULAR BIOPHYSICST32GM008403 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI BARRICK, DOUGLAS E. · 1990 to 2019
$13.5M
Live-cell Activity Architecture in CancerR35CA197622 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jin Zhang · 2015 to 2026
$11.2M
Chemical Approaches to Protein PhosphorylationR01CA074305 · NCI · JOHNS HOPKINS UNIVERSITY · PI COLE, PHILIP A · 2002 to 2025
$8.0M
Mechanisms of Compartmentalized cAMP SignalingR01DK073368 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jin Zhang · 2006 to 2026
$7.6M
Membrane Protein StabilityR01GM079440 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI FLEMING, KAREN G. · 2009 to 2022
$4.1M
Creating a Genetically Encodable Nano-Compass to Navigate in Molecular NetworksDP1CA174423 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ZHANG, JIN · 2012 to 2014
$1.6M
Probing the role of AKAPs in breast cancer using stapled peptide inhibitorsK22CA154600 · NCI · UNIVERSITY OF GEORGIA · PI KENNEDY, EILEEN J · 2011 to 2013
$571k
Direct modulation of PKA signal termination by PDE and CalcineurinF32GM120798 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GREENWALD, ERIC C · 2016 to 2018
$152k
Targeted Inhibition of EGFR DimerizationR03CA188439 · NCI · UNIVERSITY OF GEORGIA · PI KENNEDY, EILEEN J · 2015 to 2016
$150k
NCI NIH HHS DP1 CA174423NCI NIH HHS K22 CA154600NCI NIH HHS R01 CA074305NCI NIH HHS R03 CA188439NCI NIH HHS R35 CA197622NIDDK NIH HHS R01 DK073368NIGMS NIH HHS F32 GM120798NIGMS NIH HHS R01 GM079440NIGMS NIH HHS T32 GM008403
6 · The paper itself

Abstract

Compartmentalized biochemical activities are essential to all cellular processes, but there is no generalizable method to visualize dynamic protein activities in living cells at a resolution commensurate with cellular compartmentalization. Here, we introduce a new class of fluorescent biosensors that detect biochemical activities in living cells at a resolution up to threefold better than the diffraction limit. These 'FLINC' biosensors use binding-induced changes in protein fluorescence dynamics to translate kinase activities or protein-protein interactions into changes in fluorescence fluctuations, which are quantifiable through stochastic optical fluctuation imaging. A protein kinase A (PKA) biosensor allowed us to resolve minute PKA activity microdomains on the plasma membranes of living cells and to uncover the role of clustered anchoring proteins in organizing these activity microdomains. Together, these findings suggest that biochemical activities of the cell are spatially organized into an activity architecture whose structural and functional characteristics can be revealed by these new biosensors.

Indexed as

Biosensing TechniquesCell MembraneCyclic AMP-Dependent Protein KinasesEscherichia coliFluorescence Resonance Energy TransferFluorescent DyesGreen Fluorescent ProteinsHeLa CellsHumansMicroscopyMolecular ImagingMutagenesis, Site-DirectedProtein Interaction MappingStochastic ProcessesCyclic AMP-Dependent Protein KinasesFluorescent DyesGreen Fluorescent Proteins

Identifiers

PMID28288122
PMCPMC5388356
OpenAlexW2595091891

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.