Evidence mapPaperPMID 36914767Full record

ArticleCell death and differentiation2023

Doublecortin-like kinase 1 activates NF-κB to induce inflammatory responses by binding directly to IKKβ.

Wu Luo, Yiyi Jin, Yuchen Jiang, Libin Yang, Haowen Xu, Di Wu, Yanmei Zhang, Lina Yin, Zia Ali Khan, Guang Liang and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

13 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Ethanol extract ofFood science and biotechnology · 2025
    Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
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

11 authors at 4 institutions in 2 countries.

Wu LuoChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Yiyi JinChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Yuchen JiangChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Libin YangChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Haowen XuChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Di WuChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Yanmei ZhangSchool of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang, 311399, China.
Lina YinSchool of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang, 311399, China.
Zia Ali KhanDepartment of Pathology and Laboratory Medicine, University of Western Ontario, London, ON, N6A 5C1, Canada.ORCID 0000-0003-1682-5720
Guang LiangChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. wzmcliangguang@163.com.ORCID 0000-0002-8278-849X
Yi WangChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. yi.wang1122@wmu.edu.cn.ORCID 0000-0001-9048-0092
Wenzhou Medical University · CNHangzhou Medical College · CNHangzhou Normal University · CNWestern University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Doublecortin-like kinase 1 (DCLK1), a microtubule-associated protein kinase, is involved in neurogenesis, and its levels are elevated in various human cancers. Recent studies suggest that DCLK1 may relate to inflammatory responses in the mouse model of colitis. However, cellular pathways engaged by DCLK1, and potential substrates of the kinase remain undefined. To understand how DCLK1 regulates inflammatory responses, we utilized the well-established lipopolysaccharide (LPS)-stimulated macrophages and mouse model. Through a range of macrophage-based and cell-free platforms, we discovered that DCLK1 binds directly with the inhibitor of κB kinase β (IKKβ) and induces IKKβ phosphorylation on Ser177/181 to initiate nuclear factor-κB (NF-κB) pathway. Deficiency in DCLK1, achieved by silencing or through pharmacological inhibition, prevented LPS-induced NF-κB activation and cytokine production in macrophages. We further show that mice with myeloid-specific DCLK1 knockout or DCLK1 inhibitor treatment are protected against LPS-induced acute lung injury and septic death. Our studies report a novel functional role of macrophage DCLK1 as a direct IKKβ regulator in inflammatory signaling and suggest targeted therapy against DCLK1 for inflammatory diseases.

Indexed as

I-kappa B KinaseNF-kappa BAnimalsDoublecortin-Like KinasesHumansLipopolysaccharidesMicePhosphorylationProtein Serine-Threonine KinasesDCLK1 protein, humanDoublecortin-Like KinasesI-kappa B KinaseLipopolysaccharidesNF-kappa BProtein Serine-Threonine Kinases

Identifiers

PMID36914767
PMCPMC10154386
OpenAlexW4324129880

What Socratic 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 Socratic graph.