Evidence map›Paper›PMID 25100717›Full record

ArticleThe Journal of biological chemistry2014

Integrin-linked kinase modulates lipopolysaccharide- and Helicobacter pylori-induced nuclear factor κB-activated tumor necrosis factor-α production via regulation of p65 serine 536 phosphorylation.

Afsar U Ahmed, Soroush T Sarvestani, Michael P Gantier, Bryan R G Williams, Gregory E Hannigan

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
1.6field-weighted citation impact, top 19% 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

34 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Glucolipid Metabolic Disorders andInternational journal of endocrinology · 2026
    Review
  5. Article
  6. Traditional Chinese medicine in the treatment ofWorld journal of gastroenterology · 2025
    Review
  7. Review
  8. Article
  9. Article
  10. Post-translational modifications of p65: state of the art.Frontiers in cell and developmental biology · 2024
    Review
  11. Article
  12. ISGylation of NF-κBp65 by SCFArteriosclerosis, thrombosis, and vascular biology · 2023
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. 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

5 authors at 1 institution in 1 country.

Afsar U AhmedFrom the Centre for Cancer Research, MIMR-PHI Institute of Medical Research, and Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia.
Soroush T SarvestaniFrom the Centre for Cancer Research, MIMR-PHI Institute of Medical Research, and Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia.
Michael P GantierFrom the Centre for Cancer Research, MIMR-PHI Institute of Medical Research, and Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia.
Bryan R G WilliamsFrom the Centre for Cancer Research, MIMR-PHI Institute of Medical Research, and Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia bryan.williams@mimr-phi.org.
Gregory E HanniganFrom the Centre for Cancer Research, MIMR-PHI Institute of Medical Research, and Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia greg.hannigan@mimr-phi.org.
Monash University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Integrin-linked kinase (ILK) is a ubiquitously expressed and highly conserved serine-threonine protein kinase that regulates cellular responses to a wide variety of extracellular stimuli. ILK is involved in cell-matrix interactions, cytoskeletal organization, and cell signaling. ILK signaling has also been implicated in oncogenesis and progression of cancers. However, its role in the innate immune system remains unknown. Here, we show that ILK mediates pro-inflammatory signaling in response to lipopolysaccharide (LPS). Pharmacological or genetic inhibition of ILK in mouse embryonic fibroblasts and macrophages selectively blocks LPS-induced production of the pro-inflammatory cytokine tumor necrosis factor α (TNF-α). ILK is required for LPS-induced activation of nuclear factor κB (NF-κB) and transcriptional induction of TNF-α. The modulation of LPS-induced TNF-α synthesis by ILK does not involve the classical NF-κB pathway, because IκB-α degradation and p65 nuclear translocation are both unaffected by ILK inhibition. Instead, ILK is involved in an alternative activation of NF-κB signaling by modulating the phosphorylation of p65 at Ser-536. Furthermore, ILK-mediated alternative NF-κB activation through p65 Ser-536 phosphorylation also occurs during Helicobacter pylori infection in macrophages and gastric cancer cells. Moreover, ILK is required for H. pylori-induced TNF-α secretion in macrophages. Although ILK-mediated phosphorylation of p65 at Ser-536 is independent of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway during LPS stimulation, upon H. pylori infection this event is dependent on the PI3K/Akt pathway. Our findings implicate ILK as a critical regulatory molecule for the NF-κB-mediated pro-inflammatory signaling pathway, which is essential for innate immune responses against pathogenic microorganisms.

Indexed as

Amino Acid MotifsAnimalseIF-2 KinaseGene Expression RegulationHelicobacter InfectionsHelicobacter pyloriHumansLipopolysaccharidesMiceMice, Inbred C57BLNF-kappa BPhosphorylationProtein Serine-Threonine KinasesScaffold Protein ILKSerineTumor Necrosis Factor-alphaeIF-2 KinaseLipopolysaccharidesNF-kappa BProtein Serine-Threonine KinasesScaffold Protein ILKSerineTumor Necrosis Factor-alphaHelicobacter pyloriInflammationInnate ImmunityIntegrin-linked Kinase (ILK)Lipopolysaccharide (LPS)NF-kappa Bp65Phosphatidylinositide 3-Kinase (PI 3-Kinase)Small MoleculeTumor Necrosis Factor (TNF)

Identifiers

PMID25100717
PMCPMC4183813
OpenAlexW2055004859

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.