ArticleMolecular biology of the cell2013
Central role of the exchange factor GEF-H1 in TNF-α-induced sequential activation of Rac, ADAM17/TACE, and RhoA in tubular epithelial cells.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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.
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.
Who cites it
26 citing papers in PubMed, 54 citations in OpenAlex.
- Integrated Network and Transcriptomic Analyses Identify a Candidate Ethanol-ADAM17 Molecular Axis Associated with Glioblastoma Progression.International journal of molecular sciences · 2026Article
- GAK antagonises ROCK-dependent regulation of actomyosin dynamics.Journal of cell science · 2026Article
- Article
- Keratinocyte-derived VEGF-A is an essential pro-migratory autocrine mediator, acting through the KDR/GEF-H1/RhoA pathway.Frontiers in cell and developmental biology · 2025Article
- Linear motif specificity in signaling through p38α and ERK2 mitogen-activated protein kinases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Downregulation of ADAM17 in pediatric immune thrombocytopenia impairs proplatelet formation.BMC pediatrics · 2022Article
- ADAMs family in kidney physiology and pathology.EBioMedicine · 2021Review
- Kidney Adaptations Prevent Loss of Trace Elements in Wistar Rats with Early Metabolic Syndrome.Biological trace element research · 2021Article
- S-1-propenylcysteine improves TNF-α-induced vascular endothelial barrier dysfunction by suppressing the GEF-H1/RhoA/Rac pathway.Cell communication and signaling : CCS · 2021Article
- YAP and TAZ protect against white adipocyte cell death during obesity.Nature communications · 2020Article
- Claudin-2 suppresses GEF-H1, RHOA, and MRTF, thereby impacting proliferation and profibrotic phenotype of tubular cells.The Journal of biological chemistry · 2019Article
- NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells.Journal of experimental & clinical cancer research : CR · 2019Article
- The Microtubule-Associated Innate Immune Sensor GEF-H1 Does Not Influence Mouse Norovirus Replication in Murine Macrophages.Viruses · 2019Article
- iRhom2 promotes lupus nephritis through TNF-α and EGFR signaling.The Journal of clinical investigation · 2018Article
- Dynasore enhances the formation of mitochondrial antiviral signalling aggregates and endocytosis-independent NF-κB activation.British journal of pharmacology · 2015Article
- Tumor necrosis factor-α induces a biphasic change in claudin-2 expression in tubular epithelial cells: role in barrier functions.American journal of physiology. Cell physiology · 2015Article
- Dual regulation of tumor necrosis factor-α on myosin light chain phosphorylation in vascular smooth muscle.American journal of physiology. Heart and circulatory physiology · 2015Article
- Asef controls vascular endothelial permeability and barrier recovery in the lung.Molecular biology of the cell · 2015Article
- Hepatocyte growth factor-induced Asef-IQGAP1 complex controls cytoskeletal remodeling and endothelial barrier.The Journal of biological chemistry · 2015Article
- Hepatocyte growth factor triggers distinct mechanisms of Asef and Tiam1 activation to induce endothelial barrier enhancement.Cellular signalling · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Transactivation of the epidermal growth factor receptor (EGFR) by tumor necrosis factor-α (TNF-α) is a key step in mediating RhoA activation and cytoskeleton and junction remodeling in the tubular epithelium. In this study we explore the mechanisms underlying TNF-α-induced EGFR activation. We show that TNF-α stimulates the TNF-α convertase enzyme (TACE/a disintegrin and metalloproteinase-17), leading to activation of the EGFR/ERK pathway. TACE activation requires the mitogen-activated protein kinase p38, which is activated through the small GTPase Rac. TNF-α stimulates both Rac and RhoA through the guanine nucleotide exchange factor (GEF)-H1 but by different mechanisms. EGFR- and ERK-dependent phosphorylation at the T678 site of GEF-H1 is a prerequisite for RhoA activation only, whereas both Rac and RhoA activation require GEF-H1 phosphorylation on S885. Of interest, GEF-H1-mediated Rac activation is upstream from the TACE/EGFR/ERK pathway and regulates T678 phosphorylation. We also show that TNF-α enhances epithelial wound healing through TACE, ERK, and GEF-H1. Taken together, our findings can explain the mechanisms leading to hierarchical activation of Rac and RhoA by TNF-α through a single GEF. This mechanism could coordinate GEF functions and fine-tune Rac and RhoA activation in epithelial cells, thereby promoting complex functions such as sheet migration.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.