Evidence map›Paper›PMID 34413312›Full record

ArticleNature communications2021

Integration of FRET and sequencing to engineer kinase biosensors from mammalian cell libraries.

Longwei Liu, Praopim Limsakul, Xianhui Meng, Yan Huang, Reed E S Harrison, Tse-Shun Huang, Yiwen Shi, Yiyan Yu, Krit Charupanit, Sheng Zhong and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 13% 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

20 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
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  3. EchoBack-CAR T cells: Tuning immunity with sound.Clinical and translational medicine · 2025
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  13. Decoding the interplay between mScience advances · 2024
    Article
  14. Review
  15. Review
  16. Balancing activation and co-stimulation of CAR tunes signaling dynamics and enhances therapeutic potency.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  17. Review
  18. Article
  19. Resource for FRET-Based Biosensor Optimization.Frontiers in cell and developmental biology · 2022
    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 4 institutions in 3 countries.

Longwei Liu *Department of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, CA, USA.
Praopim Limsakul *Department of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, CA, USA.
Xianhui Meng *Department of Cell Biology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, P.R. China.
Yan HuangDepartment of Chemistry and Chemical Engineering, Hunan University, Changsha, P.R. China.
Reed E S HarrisonDepartment of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, CA, USA.ORCID 0000-0003-2512-4344
Tse-Shun HuangDepartment of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, CA, USA.
Yiwen ShiDepartment of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, CA, USA.
Yiyan YuDepartment of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, CA, USA.
Krit CharupanitDepartment of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.ORCID 0000-0002-9803-2005
Sheng ZhongDepartment of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, CA, USA.
Shaoying LuDepartment of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, CA, USA.
Jin ZhangDepartment of Pharmacology, University of California, San Diego, CA, USA.
Shu ChienDepartment of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, CA, USA.
Jie SunDepartment of Cell Biology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, P.R. China. sunj4@zju.edu.cn.ORCID 0000-0002-5642-0560
Yingxiao WangDepartment of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, CA, USA. yiw015@eng.ucsd.edu.ORCID 0000-0003-0265-326X
University of California San Diego · USFirst Affiliated Hospital Zhejiang University · CNPrince of Songkla University · THHunan University · CN

Funding

Live-cell Activity Architecture in CancerR35CA197622 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jin Zhang · 2015 to 2026
$11.2M
Role of Spatiotemporal Epigenetic Dynamics in Regulating Endothelial Gene Expressions under FlowsR01HL121365 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHIEN, SHU, WANG, YINGXIAO · 2014 to 2025
$7.5M
ELECTRON SPIN RELAXATION IN MODEL MEMBRANESR01EB003150 · NIBIB · CORNELL UNIVERSITY ITHACA · PI FREED, JACK H · 2005 to 2016
$4.9M
Extremely high-throughput mapping of protein, RNA, and chromatin interactions in health and diseaseDP1DK126138 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ZHONG, SHENG · 2020 to 2024
$3.7M
Acoustothermogenetics for Cell EngineeringR35GM140929 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI WANG, YINGXIAO · 2021 to 2025
$2.9M
Locus-specific Imaging of Dynamic Histone Methylations during ReprogrammingR01GM125379 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, WANG, YINGXIAO · 2017 to 2020
$2.4M
New tools for quantitative non-invasive recording of biochemical signalsR01CA279813 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jennifer Prescher, Nathan Christopher Shaner · 2024 to 2026
$2.0M
Revealing protein-protein interactions and RNA-protein interactions at genome-scale in two weeksR01GM138852 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ZHONG, SHENG · 2020 to 2023
$1.5M
Multiplex FRET Imaging of Kinase-Epigenome Interregulations in Live Cancer CellsR33CA204704 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WANG, YINGXIAO · 2017 to 2019
$1.1M
Remote-Control Mechano-Genetics and Epigenetics for Live Cell ManipulationR01GM126016 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WANG, YINGXIAO · 2018 to 2020
$1.1M
NCI NIH HHS R01 CA279813NCI NIH HHS R33 CA204704NCI NIH HHS R35 CA197622NHLBI NIH HHS R01 HL121365NIBIB NIH HHS R01 EB003150NIDDK NIH HHS DP1 DK126138NIGMS NIH HHS R01 GM125379NIGMS NIH HHS R01 GM126016NIGMS NIH HHS R01 GM138852NIGMS NIH HHS R35 GM140929
6 · The paper itself

Abstract

The limited sensitivity of Förster Resonance Energy Transfer (FRET) biosensors hinders their broader applications. Here, we develop an approach integrating high-throughput FRET sorting and next-generation sequencing (FRET-Seq) to identify sensitive biosensors with varying substrate sequences from large-scale libraries directly in mammalian cells, utilizing the design of self-activating FRET (saFRET) biosensor. The resulting biosensors of Fyn and ZAP70 kinases exhibit enhanced performance and enable the dynamic imaging of T-cell activation mediated by T cell receptor (TCR) or chimeric antigen receptor (CAR), revealing a highly organized ZAP70 subcellular activity pattern upon TCR but not CAR engagement. The ZAP70 biosensor elucidates the role of immunoreceptor tyrosine-based activation motif (ITAM) in affecting ZAP70 activation to regulate CAR functions. A saFRET biosensor-based high-throughput drug screening (saFRET-HTDS) assay further enables the identification of an FDA-approved cancer drug, Sunitinib, that can be repurposed to inhibit ZAP70 activity and autoimmune-disease-related T-cell activation.

Indexed as

Biosensing TechniquesCells, CulturedFluorescence Resonance Energy TransferHigh-Throughput Nucleotide SequencingHumansPhosphotransferasesProtein EngineeringProto-Oncogene Proteins c-fynT-LymphocytesZAP-70 Protein-Tyrosine KinaseFYN protein, humanPhosphotransferasesProto-Oncogene Proteins c-fynZAP70 protein, humanZAP-70 Protein-Tyrosine Kinase

Identifiers

PMID34413312
PMCPMC8376904
OpenAlexW3193286140

What Socratic 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 Socratic graph.