Evidence map›Paper›PMID 41003242›Full record

ArticleThe Biochemical journal2025

Unconventional binding of calmodulin to CHK2 kinase inhibits catalytic activity.

Christopher R Horne, Tingting Wang, Samuel N Young, Toby A Dite, Hunter G Nyvall, Sushant Suresh, Katherine A Davies, Abner Gonzalez Castro, Vineet Vaibhav, Lucy J Mather and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Biochemical journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. PSKH1 kinase activity is differentially modulated via allosteric binding of CaProceedings of the National Academy of Sciences of the United States of America · 2025
    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

18 authors.

Christopher R HorneWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3052, Australia.ORCID 0000-0003-1318-514X
Tingting WangCollege of Medicine and Public Health, Flinders University, Adelaide, South Australia, 5001, Australia.
Samuel N YoungWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3052, Australia.
Toby A DiteWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3052, Australia.
Hunter G NyvallDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
Sushant SureshDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
Katherine A DaviesWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3052, Australia.
Abner Gonzalez CastroWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3052, Australia.
Vineet VaibhavWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3052, Australia.
Lucy J MatherWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3052, Australia.
Laura F DagleyWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3052, Australia.
Matthew J BelousoffDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Victoria, 3052, Australia.
Gerard ManningNuaBio Research, Burlingame, 94010, CA, U.S.A.
Anthony R MeansMolecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, U.S.A.
John E BurkeDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
Janni PetersenCollege of Medicine and Public Health, Flinders University, Adelaide, South Australia, 5001, Australia.
John W Scott *Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Victoria, 3052, Australia.ORCID 0000-0002-1896-9798
James M MurphyWalter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3052, Australia.ORCID 0000-0003-0195-3949

Funding

National Health and Medical Research Council 1172929, 2034104, 9000719, 2034044, 2001817
6 · The paper itself

Abstract

Calmodulin (CaM) serves an essential role in eukaryotic cells as a Ca2+ sensor. Ca2+ binding leads to conformation changes in CaM that enable engagement of a repertoire of enzymes and the regulation of their catalytic activities. Classically, Ca2+-CaM binds to an inhibitory pseudosubstrate sequence C-terminal to the kinase domain in members of the Ca2+-CaM-dependent protein kinase (CAMK) family and relieves inhibition to promote catalytic activity. Here, we report an unexpected mechanism by which CaM can bind CHK2 kinase to inhibit its kinase activity. Using biochemical, biophysical and structural mass spectrometry, we identify a direct interaction of Ca2+-CaM with the CHK2 kinase domain that suppresses CHK2 catalytic activity in vitro and identify K373 in CHK2 as crucial for cell proliferation in human cells following DNA damage. Our findings add direct suppression of kinase activity to the repertoire of CaM's functions, complementing the paradigmatic mechanism of promoting kinase activity through autoinhibitory domain sequestration.

Indexed as

CalmodulinCheckpoint Kinase 2CalciumCell ProliferationDNA DamageHumansProtein BindingProtein DomainsCalciumCalmodulinCheckpoint Kinase 2CHEK2 protein, humanallosteric regulationcalcium signallingcalmodulincell cyclekinases

Identifiers

PMID41003242
PMCPMC12751073

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.