Evidence map›Paper›PMID 28735895›Full record

ArticleMolecular cell2017

A Phosphosite within the SH2 Domain of Lck Regulates Its Activation by CD45.

Adam H Courtney, Jeanine F Amacher, Theresa A Kadlecek, Marianne N Mollenauer, Byron B Au-Yeung, John Kuriyan, Arthur Weiss

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

45 citing papers in PubMed, 72 citations in OpenAlex.

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  10. Construction of a pathway-level model for preeclampsia based on gene expression data.Hypertension research : official journal of the Japanese Society of Hypertension · 2024
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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

7 authors at 3 institutions in 1 country.

Adam H CourtneyDivision of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Jeanine F AmacherDepartments of Molecular and Cell Biology and Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
Theresa A KadlecekThe Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 04143, USA.
Marianne N MollenauerThe Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 04143, USA.
Byron B Au-YeungDivision of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
John KuriyanDepartments of Molecular and Cell Biology and Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA; The Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Arthur WeissDivision of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; The Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 04143, USA. Electronic address: aweiss@medicine.ucsf.edu.
Howard Hughes Medical Institute · USUniversity of California, San Francisco · USUniversity of California, Berkeley · US

Funding

Understand the metabolic fitness of naïve T cellsP01AI091580 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ARTHUR Robert SALOMON · 2011 to 2026
$31.1M
Inhibition of ZAP-70 to selectively attenuate autoimmune disease-inducing T cellsK01AR065481 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AU-YEUNG, BYRON BENTON · 2014 to 2016
$385k
NIAID NIH HHS P01 AI091580NIAMS NIH HHS K01 AR065481
6 · The paper itself

Abstract

The Src Family kinase Lck sets a critical threshold for T cell activation because it phosphorylates the TCR complex and the Zap70 kinase. How a T cell controls the abundance of active Lck molecules remains poorly understood. We have identified an unappreciated role for a phosphosite, Y192, within the Lck SH2 domain that profoundly affects the amount of active Lck in cells. Notably, mutation of Y192 blocks critical TCR-proximal signaling events and impairs thymocyte development in retrogenic mice. We determined that these defects are caused by hyperphosphorylation of the inhibitory C-terminal tail of Lck. Our findings reveal that modification of Y192 inhibits the ability of CD45 to associate with Lck in cells and dephosphorylate the C-terminal tail of Lck, which prevents its adoption of an active open conformation. These results suggest a negative feedback loop that responds to signaling events that tune active Lck amounts and TCR sensitivity.

Indexed as

src Homology DomainsAnimalsEnzyme ActivationGenotypeHEK293 CellsHumansJurkat CellsLeukocyte Common AntigensLymphocyte Specific Protein Tyrosine Kinase p56(lck)Mice, Inbred C57BLMice, KnockoutModels, MolecularMutationPhenotypePhosphorylationProtein BindingFyn protein, mouseLeukocyte Common AntigensLymphocyte Specific Protein Tyrosine Kinase p56(lck)Proto-Oncogene Proteins c-fynPTPRC protein, humanPtprc protein, mouseReceptors, Antigen, T-CellCD45kinaseLckphosphatasephosphorylationSH2 domainSrc family kinaseT cell antigen receptorT cell signalingTCR

Identifiers

PMID28735895
PMCPMC5558854
OpenAlexW2737071436

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.