Evidence map›Paper›PMID 10064600›Full record

ArticleThe EMBO journal1999

TGF-beta induces fibronectin synthesis through a c-Jun N-terminal kinase-dependent, Smad4-independent pathway.

B A Hocevar, T L Brown, P H Howe

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 220 papers.

0numbers the graph read from it
0cells of the map it votes in
220citing papers in PubMed
19.0field-weighted citation impact, top 1% 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

220 citing papers in PubMed, 674 citations in OpenAlex.

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  14. TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024
    Review
  15. Article
  16. SMAD4: A critical regulator of cardiac neural crest cell fate and vascular smooth muscle development.Developmental dynamics : an official publication of the American Association of Anatomists · 2024
    Article
  17. Article
  18. Article
  19. Article
  20. Article

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

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

3 authors at 1 institution in 1 country.

B A HocevarDepartment of Cell Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
T L Brown
P H Howe
Cleveland Clinic · US

Funding

TRANSFORMING GROWTH FACTOR BETA SIGNALING PATHWAYSR01CA055536 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HOWE, PHILIP H · 1997 to 2017
$5.0M
CELL CYLCE REGULATION OF EPITHELIAL CELL GROWTHR29CA055536 · NCI · CLEVELAND CLINIC FOUNDATION · PI HOWE, PHILIP H · 1992 to 1996
–
NCI NIH HHS CA55536
6 · The paper itself

Abstract

Transforming growth factor-beta (TGF-beta) exerts its effects on cell proliferation, differentiation and migration in part through its modulation of extracellular matrix components, such as fibronectin and plasminogen activator inhibitor-1 (PAI-1). Although the SMAD family of proteins recently has been shown to be a key participant in TGF-beta signaling, other signaling pathways have also been shown to be activated by TGF-beta. We report here that c-Jun N-terminal kinase (JNK), a member of the MAP kinase family, is activated in response to TGF-beta in the human fibrosarcoma HT1080-derived cell line BAHgpt. Stable expression of dominant-negative forms of JNK1 and MKK4, an upstream activator of JNK, results in loss of TGF-beta-stimulated fibronectin mRNA and protein induction, while having little effect on TGF-beta-induced levels of PAI-1. The human fibronectin promoter contains three CRE elements, one of which has been shown to bind a c-Jun-ATF-2 heterodimer. Utilizing a GAL4 fusion trans-reporting system, we demonstrate a decrease in transactivating potential of GAL4-c-Jun and GAL4-ATF-2 in dominant-negative JNK1- and MKK4-expressing cells. Finally, we show that TGF-beta-induced fibronectin synthesis is independent of Smad4. These results demonstrate that TGF-beta-mediated fibronectin induction requires activation of JNK which in turn modulates the activity of c-Jun and ATF-2 in a Smad4independent manner.

Indexed as

MAP Kinase Kinase 4Mitogen-Activated Protein Kinase KinasesMitogen-Activated Protein KinasesCalcium-Calmodulin-Dependent Protein KinasesDNA-Binding ProteinsEnzyme ActivationEnzyme InhibitorsFibronectinsGene Expression RegulationGenes, ReporterHumansJNK Mitogen-Activated Protein KinasesProtein Serine-Threonine KinasesProtein-Tyrosine KinasesRecombinant Fusion ProteinsRNA, MessengerCalcium-Calmodulin-Dependent Protein KinasesDNA-Binding ProteinsEnzyme InhibitorsFibronectinsJNK Mitogen-Activated Protein KinasesMAP2K4 protein, humanMAP Kinase Kinase 4Mitogen-Activated Protein Kinase KinasesMitogen-Activated Protein KinasesProtein Serine-Threonine KinasesProtein-Tyrosine KinasesRecombinant Fusion ProteinsRNA, MessengerSmad4 ProteinSMAD4 protein, humanTrans-ActivatorsTransforming Growth Factor beta

Identifiers

PMID10064600
PMCPMC1171224
OpenAlexW2100398824

What OpenQuestion holds

Texttitle and abstract
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.