Evidence map›Paper›PMID 29083415›Full record

ArticleNature structural & molecular biology2017

Encoding optical control in LCK kinase to quantitatively investigate its activity in live cells.

Ardiyanto Liaunardy-Jopeace, Ben L Murton, Mohan Mahesh, Jason W Chin, John R James

Open access · greenAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

43 citing papers in PubMed, 65 citations in OpenAlex.

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  13. Expanding the Genetic Code ofACS chemical biology · 2024
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  18. Self-programmed dynamics of T cell receptor condensation.Proceedings of the National Academy of Sciences of the United States of America · 2023
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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

5 authors at 2 institutions in 1 country.

Ardiyanto Liaunardy-JopeaceMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC-LMB, Cambridge, UK.
Ben L MurtonMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC-LMB, Cambridge, UK.
Mohan MaheshMedical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK.
Jason W ChinMedical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK.ORCID http://orcid.org/0000-0003-1219-4757
John R JamesMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC-LMB, Cambridge, UK.ORCID http://orcid.org/0000-0003-1452-7578
University of Cambridge · GBMRC Laboratory of Molecular Biology · GB

Funding

Medical Research Council MC_U105181009Medical Research Council MC_UP_A024_1008Wellcome Trust 099966
6 · The paper itself

Abstract

LCK is a tyrosine kinase that is essential for initiating T-cell antigen receptor (TCR) signaling. A complete understanding of LCK function is constrained by a paucity of methods to quantitatively study its function within live cells. To address this limitation, we generated LCK*, in which a key active-site lysine is replaced by a photocaged equivalent, using genetic code expansion. This strategy enabled fine temporal and spatial control over kinase activity, thus allowing us to quantify phosphorylation kinetics in situ using biochemical and imaging approaches. We find that autophosphorylation of the LCK active-site loop is indispensable for its catalytic activity and that LCK can stimulate its own activation by adopting a more open conformation, which can be modulated by point mutations. We then show that CD4 and CD8, T-cell coreceptors, can enhance LCK activity, thereby helping to explain their effect in physiological TCR signaling. Our approach also provides general insights into SRC-family kinase dynamics.

Indexed as

Catalytic DomainCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell LineEnzyme ActivationHEK293 CellsHumansLymphocyte Specific Protein Tyrosine Kinase p56(lck)PhosphorylationReceptors, Antigen, T-CellSignal TransductionZAP-70 Protein-Tyrosine KinaseLymphocyte Specific Protein Tyrosine Kinase p56(lck)Receptors, Antigen, T-CellZAP70 protein, humanZAP-70 Protein-Tyrosine Kinase

Identifiers

PMID29083415
PMCPMC5736103
OpenAlexW2765968231

What OpenQuestion holds

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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.