Evidence map›Paper›PMID 24945436›Full record

ArticlePLoS pathogens2014

The calcium-dependent protein kinase 3 of toxoplasma influences basal calcium levels and functions beyond egress as revealed by quantitative phosphoproteome analysis.

Moritz Treeck, John L Sanders, Rajshekhar Y Gaji, Kacie A LaFavers, Matthew A Child, Gustavo Arrizabalaga, Joshua E Elias, John C Boothroyd

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.0field-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

47 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
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  4. Review
  5. Article
  6. Proteomics Applications inPathogens (Basel, Switzerland) · 2023
    Review
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  9. Identification ofmSphere · 2023
    Article
  10. Article
  11. mSphere · 2022
    Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Protein kinases in Toxoplasma gondii.International journal for parasitology · 2021
    Review
  17. Article
  18. Article
  19. Article
  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

8 authors at 2 institutions in 1 country.

Moritz TreeckDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.
John L SandersDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California, United States of America.
Rajshekhar Y GajiDepartment of Pharmacology and Toxicology, School of Medicine, University of Indianapolis, Indianapolis, Indiana, United States of America.
Kacie A LaFaversDepartment of Pharmacology and Toxicology, School of Medicine, University of Indianapolis, Indianapolis, Indiana, United States of America.
Matthew A ChildDepartment of Pathology, Stanford University School of Medicine, Stanford, California, United States of America.
Gustavo ArrizabalagaDepartment of Pharmacology and Toxicology, School of Medicine, University of Indianapolis, Indianapolis, Indiana, United States of America.
Joshua E EliasDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California, United States of America.
John C BoothroydDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.
Stanford University · USUniversity of Indianapolis · US

Funding

Immunology and Infectious Diseases Training ProgramT32AI060519 · NIAID · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI MARK H KAPLAN · 2004 to 2026
$6.0M
Phosphoproteome of ToxoplasmaR21AI097633 · NIAID · STANFORD UNIVERSITY · PI BOOTHROYD, JOHN C · 2012 to 2013
$430k
The protective role of kidney-derived Tamm Horsfall protein (Uromodulin) in sepsisK99DK127216 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI LAFAVERS, KAICE · 2021 to 2022
$179k
Characterization of calcium signaling proteins in Toxoplasma gondiiR03AI101624 · NIAID · INDIANA UNIVERSITY INDIANAPOLIS · PI ARRIZABALAGA, GUSTAVO A · 2012 to 2013
$156k
NIAID NIH HHS AI097633NIAID NIH HHS AI 101624NIAID NIH HHS R03 AI101624NIAID NIH HHS R21 AI097633NIAID NIH HHS T32 AI060519NIDDK NIH HHS K99 DK127216
6 · The paper itself

Abstract

Calcium-dependent protein kinases (CDPKs) are conserved in plants and apicomplexan parasites. In Toxoplasma gondii, TgCDPK3 regulates parasite egress from the host cell in the presence of a calcium-ionophore. The targets and the pathways that the kinase controls, however, are not known. To identify pathways regulated by TgCDPK3, we measured relative phosphorylation site usage in wild type and TgCDPK3 mutant and knock-out parasites by quantitative mass-spectrometry using stable isotope-labeling with amino acids in cell culture (SILAC). This revealed known and novel phosphorylation events on proteins predicted to play a role in host-cell egress, but also a novel function of TgCDPK3 as an upstream regulator of other calcium-dependent signaling pathways, as we also identified proteins that are differentially phosphorylated prior to egress, including proteins important for ion-homeostasis and metabolism. This observation is supported by the observation that basal calcium levels are increased in parasites where TgCDPK3 has been inactivated. Most of the differential phosphorylation observed in CDPK3 mutants is rescued by complementation of the mutants with a wild type copy of TgCDPK3. Lastly, the TgCDPK3 mutants showed hyperphosphorylation of two targets of a related calcium-dependent kinase (TgCDPK1), as well as TgCDPK1 itself, indicating that this latter kinase appears to play a role downstream of TgCDPK3 function. Overexpression of TgCDPK1 partially rescues the egress phenotype of the TgCDPK3 mutants, reinforcing this conclusion. These results show that TgCDPK3 plays a pivotal role in regulating tachyzoite functions including, but not limited to, egress.

Indexed as

CalciumCalcium-Calmodulin-Dependent Protein KinasesCalcium SignalingGene Knockout TechniquesPhosphorylationProtein KinasesProteomeProtozoan ProteinsToxoplasmaCalciumCalcium-Calmodulin-Dependent Protein KinasesProtein KinasesProteomeProtozoan Proteins

Identifiers

PMID24945436
PMCPMC4063958
OpenAlexW2016580837

What OpenQuestion 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 OpenQuestion graph.