Evidence map›Paper›PMID 24832449›Full record

ArticleCell host & microbe2014

The Toxoplasma pseudokinase ROP5 forms complexes with ROP18 and ROP17 kinases that synergize to control acute virulence in mice.

Ronald D Etheridge, Aditi Alaganan, Keliang Tang, Hua Jane Lou, Benjamin E Turk, L David Sibley

Abstract read
In one paragraph

Article in Cell host & microbe, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.

0numbers the graph read from it
0cells of the map it votes in
160citing 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

160 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Cysteine-S-nitrosylation inhibits Rop5-mediated immune evasion inbioRxiv : the preprint server for biology · 2025
    Article
  5. Article
  6. Comparative genomic analysis of fiveMicrobial genomics · 2025
    Article
  7. Article
  8. Mapping amBio · 2025
    Article
  9. Article
  10. Article
  11. Vaccines · 2025
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. NcROP2 deletion reducesFrontiers in immunology · 2025
    Article
  18. Article
  19. Article
  20. International journal of molecular sciences · 2024
    Article

100 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Ronald D EtheridgeDepartment of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Aditi AlagananDepartment of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Keliang TangDepartment of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Hua Jane LouDepartment of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Benjamin E TurkDepartment of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
L David SibleyDepartment of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. Electronic address: sibley@wustl.edu.

Funding

Washington University DDRCC Supplemental Equipment RequestP30DK052574 · NIDDK · WASHINGTON UNIVERSITY · PI Nicholas O. Davidson · 2000 to 2026
$30.8M
MOLECULAR BASIS OF TOXOPLASMOSIS IN AIDS PATIENTSR01AI036629 · NIAID · WASHINGTON UNIVERSITY · PI SIBLEY, L. DAVID · 1994 to 2013
$5.3M
TARGETING ESSENTIAL ROP KINASES IN TOXOPLASMAR01AI082423 · NIAID · WASHINGTON UNIVERSITY · PI SIBLEY, L. DAVID · 2009 to 2015
$2.9M
Modeling human phosphorylation networks through kinome-wide profilingR01GM104047 · NIGMS · YALE UNIVERSITY · PI TURK, BENJAMIN E, YAFFE, MICHAEL B · 2013 to 2017
$2.4M
CHARACTERIZATION OF ESSENTIAL RHOPTRY KINASES OF TOXOPLASMA GONDIIF32AI096853 · NIAID · WASHINGTON UNIVERSITY · PI ETHERIDGE, RONALD DREW · 2011 to 2013
$155k
NIAID NIH HHS AI036629NIAID NIH HHS AI082423NIAID NIH HHS F32 AI096853NIAID NIH HHS F32 AI096853-02NIAID NIH HHS R01 AI036629NIAID NIH HHS R01 AI082423NIDDK NIH HHS P30 DK052574NIDDK NIH HHS P30 DK52574NIGMS NIH HHS GM104047NIGMS NIH HHS R01 GM104047
6 · The paper itself

Abstract

Polymorphic rhoptry-secreted kinases (ROPs) are essential virulence factors of Toxoplasma gondii. In particular, the pseudokinase ROP5 is the major determinant of acute virulence in mice, but the underlying mechanisms are unclear. We developed a tandem affinity protein tagging and purification approach in T. gondii and used it to show that ROP5 complexes with the active kinases ROP18 and ROP17. Biochemical analyses indicate that ROP18 and ROP17 have evolved to target adjacent and essential threonine residues in switch region I of immunity-related guanosine triphosphatases (GTPases) (IRGs), a family of host defense molecules that function to control intracellular pathogens. The combined activities of ROP17 and ROP18 contribute to avoidance of IRG recruitment to the intracellular T. gondii-containing vacuole, thus protecting the parasite from clearance in interferon-activated macrophages. These studies reveal an intricate, multilayered parasite survival strategy involving pseudokinases that regulate multiple active kinase complexes to synergistically thwart innate immunity.

Indexed as

Amino Acid SequenceAnimalsGTP PhosphohydrolasesHost-Parasite InteractionsHumansMiceMolecular Sequence DataProtein BindingProtein Serine-Threonine KinasesProtozoan ProteinsSequence AlignmentToxoplasmaToxoplasmosisVirulenceVirulence FactorsGTP PhosphohydrolasesProtein Serine-Threonine KinasesProtozoan Proteinsrhoptry protein 17, Toxoplasma gondiiVirulence Factors

Identifiers

PMID24832449
PMCPMC4086214

What OpenQuestion holds

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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.