Evidence map›Paper›PMID 25118589›Full record

ArticleNature communications2014

RasGRP3 limits Toll-like receptor-triggered inflammatory response in macrophages by activating Rap1 small GTPase.

Songqing Tang, Taoyong Chen, Zhou Yu, Xuhui Zhu, Mingjin Yang, Bin Xie, Nan Li, Xuetao Cao, Jianli Wang

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 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
2.4field-weighted citation impact, top 11% 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, 58 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Divergent Functions of Rap1A and Rap1B in Endothelial Biology and Disease.International journal of molecular sciences · 2025
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Epac-2 ameliorates spontaneous colitis in Il-10Journal of cellular and molecular medicine · 2022
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Integration of Rap1 and Calcium Signaling.International journal of molecular sciences · 2020
    Review
  20. 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

9 authors at 2 institutions in 1 country.

Songqing Tang1] Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China [2] National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China [3].
Taoyong Chen1] National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China [2].
Zhou YuInstitute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Xuhui ZhuNational Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
Mingjin Yang1] National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China [2] National Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
Bin XieInstitute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Nan LiNational Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
Xuetao Cao1] Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China [2] National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China [3] National Key Laboratory of Medical Molecular Biology and Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
Jianli WangInstitute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Second Military Medical University · CNZhejiang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Host immune cells can detect and destruct invading pathogens via pattern-recognition receptors. Small Rap GTPases act as conserved molecular switches coupling extracellular signals to various cellular responses, but their roles as regulators in Toll-like receptor (TLR) signalling have not been fully elucidated. Here we report that Ras guanine nucleotide-releasing protein 3 (RasGRP3), a guanine nucleotide-exchange factor activating Ras and Rap1, limits production of proinflammatory cytokines (especially IL-6) in macrophages by activating Rap1 on activation by low levels of TLR agonists. We demonstrate that RasGRP3, a dominant member of RasGRPs in macrophages, impairs TLR3/4/9-induced IL-6 production and relieves dextrane sulphate sodium-induced colitis and collagen-induced arthritis. In RasGRP3-deficient RAW264.7 cells obtained by CRISPR-Cas9 genome editing, TLR3/4/9-induced activation of Rap1 was inhibited while ERK1/2 activation was enhanced. Our study suggests that RasGRP3 limits inflammatory response by activating Rap1 on low-intensity pathogen infection, setting a threshold for preventing excessive inflammatory response.

Indexed as

AnimalsArthritis, ExperimentalCells, CulturedDisease Models, AnimalGTP PhosphohydrolasesInflammationInterleukin-6MacrophagesMiceMice, Inbred C57BLMice, Knockoutrap1 GTP-Binding Proteinsras Guanine Nucleotide Exchange FactorsSignal TransductionToll-Like Receptor 3Toll-Like Receptor 4GTP PhosphohydrolasesInterleukin-6rap1 GTP-Binding ProteinsRasGRP3 protein, mouseras Guanine Nucleotide Exchange FactorsTLR3 protein, mouseTlr4 protein, mouseTlr9 protein, mouseToll-Like Receptor 3Toll-Like Receptor 4Toll-Like Receptor 9Toll-Like Receptors

Identifiers

PMID25118589
PMCPMC4143924
OpenAlexW2002953250

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.