Evidence map›Paper›PMID 14989696›Full record

ArticleThe Biochemical journal2004

Parasite-specific eIF2 (eukaryotic initiation factor-2) kinase required for stress-induced translation control.

William J Sullivan, Jana Narasimhan, Micah M Bhatti, Ronald C Wek

Open access · bronzeAbstract read
In one paragraph

Article in The Biochemical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
2.0field-weighted citation impact, top 16% 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

55 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. mSphere · 2022
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. A Comparison of Stage Conversion in the Coccidian ApicomplexansFrontiers in cellular and infection microbiology · 2020
    Review
  16. Article
  17. Article
  18. Effects of PERK eIF2α Kinase Inhibitor against Toxoplasma gondii.Antimicrobial agents and chemotherapy · 2018
    Article
  19. A latent ability to persist: differentiation in Toxoplasma gondii.Cellular and molecular life sciences : CMLS · 2018
    Review
  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

4 authors at 1 institution in 1 country.

William J SullivanDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, 635 Barnhill Drive, Medical Sciences Bldg, Indianapolis, IN 46202, USA. wjsulliv@iupui.edu
Jana Narasimhan
Micah M Bhatti
Ronald C Wek
Indiana University – Purdue University Indianapolis · US

Funding

Metabolic stress responses andeIF2 kinase GCN2R01GM049164 · NIGMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI WEK, RONALD C · 1998 to 2019
$6.3M
GCN5-mediated transcription in AIDS pathogen ToxoplasmaR01GM065051 · NIGMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SULLIVAN, WILLIAM J · 2003 to 2007
$1.2M
NIGMS NIH HHS R01GM065051NIGMS NIH HHS R01GM49164NIGMS NIH HHS R01GM643540
6 · The paper itself

Abstract

The ubiquitous intracellular parasite Toxoplasma gondii (phylum Apicomplexa) differentiates into an encysted form (bradyzoite) that can repeatedly re-emerge as a life-threatening acute infection (tachyzoite) upon impairment of immunity. Since the switch from tachyzoite to bradyzoite is a stress-induced response, we sought to identify components related to the phosphorylation of the alpha subunit of eIF2 (eukaryotic initiation factor-2), a well-characterized event associated with stress remediation in other eukaryotic systems. In addition to characterizing Toxoplasma eIF2alpha (TgIF2alpha), we have discovered a novel eIF2 protein kinase, designated TgIF2K-A (Toxoplasma gondii initiation factor-2kinase). Although the catalytic domain of TgIF2K-A contains sequence and structural features that are conserved among members of the eIF2 kinase family, TgIF2K-A has an extended N-terminal region that is highly divergent from other eIF2 kinases. TgIF2K-A specifically phosphorylates the regulatory serine residue of yeast eIF2alpha in vitro and in vivo, and can modulate translation when expressed in the yeast model system. We also demonstrate that TgIF2K-A phosphorylates the analogous regulatory serine residue of recombinant TgIF2alpha in vitro. Finally, we demonstrate that TgIF2alpha phosphorylation in tachyzoites is enhanced in response to heat shock or alkaline stress, conditions known to induce parasite differentiation in vitro. Collectively, this study suggests that eIF2 kinase-mediated stress responses are conserved in Apicomplexa, and a novel family member exists that may control parasite-specific events, including the clinically relevant conversion into bradyzoite cysts.

Indexed as

Amino Acid SequenceAnimalsCloning, MoleculareIF-2 KinaseEukaryotic Initiation Factor-2Metamorphosis, BiologicalMolecular Sequence DataPeptide SynthasesPhosphorylationProtein BiosynthesisProtein Serine-Threonine KinasesProtozoan ProteinsSequence AlignmentSpecies SpecificityToxoplasmaeIF-2 KinaseEukaryotic Initiation Factor-2eukaryotic initiation factor-2 alpha, Toxoplasma gondiiinitiation factor-2 kinase, Toxoplasma gondiiPeptide SynthasesProtein Serine-Threonine KinasesProtozoan Proteins

Identifiers

PMID14989696
PMCPMC1224182
OpenAlexW1996196432

What OpenQuestion holds

Textmetadata
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.