ArticleThe Journal of biological chemistry2011
The epidermal growth factor receptor mediates tumor necrosis factor-alpha-induced activation of the ERK/GEF-H1/RhoA pathway in tubular epithelium.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 75 citations in OpenAlex.
- Decoupling actin assembly from microtubule disassembly by TBC1D3C-mediated direct GEF-H1 activation.Life science alliance · 2025Article
- 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
- Bone resorption by osteoclasts involves fine tuning of RHOA activity by its microtubule-associated exchange factor GEF-H1.Frontiers in physiology · 2024Article
- Therapeutic Validation of GEF-H1 Using a De Novo Designed Inhibitor in Models of Retinal Disease.Cells · 2022Article
- Two Motors and One Spring: Hypothetic Roles of Non-Muscle Myosin II and Submembrane Actin-Based Cytoskeleton in Cell Volume Sensing.International journal of molecular sciences · 2021Review
- The Crossroads between RAS and RHO Signaling Pathways in Cellular Transformation, Motility and Contraction.Genes · 2021Review
- Contribution of ADAM17 and related ADAMs in cardiovascular diseases.Cellular and molecular life sciences : CMLS · 2021Review
- TNF-α-induced sympathetic excitation requires EGFR and ERK1/2 signaling in cardiovascular regulatory regions of the forebrain.American journal of physiology. Heart and circulatory physiology · 2021Article
- Receptor tyrosine kinase ligands and inflammatory cytokines cooperatively suppress the fibrogenic activity in temporomandibular-joint-derived fibroblast-like synoviocytes via mitogen-activated protein kinase kinase/extracellular signal-regulated kinase.Experimental and therapeutic medicine · 2020Article
- Measuring Cell Growth and Junction Development in Epithelial Cells Using Electric Cell-Substrate Impedance Sensing (ECIS).Bio-protocol · 2020Article
- EGFR activation attenuates the mechanical threshold for integrin tension and focal adhesion formation.Journal of cell science · 2020Article
- Go with the flow: GEF-H1 mediated shear stress mechanotransduction in neutrophils.Small GTPases · 2020Review
- Death receptor 5 contributes to cardiomyocyte hypertrophy through epidermal growth factor receptor transactivation.Journal of molecular and cellular cardiology · 2019Article
- Claudin-2 suppresses GEF-H1, RHOA, and MRTF, thereby impacting proliferation and profibrotic phenotype of tubular cells.The Journal of biological chemistry · 2019Article
- Assessment of the nitrofen model of congenital diaphragmatic hernia and of the dysregulated factors involved in pulmonary hypoplasia.Pediatric surgery international · 2019Article
- The BH3-only protein BAD mediates TNFα cytotoxicity despite concurrent activation of IKK and NF-κB in septic shock.Cell research · 2018Article
- Exposure to 4100K fluorescent light elicits sex specific transcriptional responses in Xiphophorus maculatus skin.Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · 2018Article
- Hair growth is promoted by BeauTop via expression of EGF and FGF‑7.Molecular medicine reports · 2018Article
- iRhom2 promotes lupus nephritis through TNF-α and EGFR signaling.The Journal of clinical investigation · 2018Article
- MMP inhibitor Ilomastat induced amoeboid-like motility via activation of the Rho signaling pathway in glioblastoma cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Tumor necrosis factor (TNF)-α induces cytoskeleton and intercellular junction remodeling in tubular epithelial cells; the underlying mechanisms, however, are incompletely explored. We have previously shown that ERK-mediated stimulation of the RhoA GDP/GTP exchange factor GEF-H1/Lfc is critical for TNF-α-induced RhoA stimulation. Here we investigated the upstream mechanisms of ERK/GEF-H1 activation. Surprisingly, TNF-α-induced ERK and RhoA stimulation in tubular cells were prevented by epidermal growth factor receptor (EGFR) inhibition or silencing. TNF-α also enhanced phosphorylation of the EGFR. EGF treatment mimicked the effects of TNF-α, as it elicited potent, ERK-dependent GEF-H1 and RhoA activation. Moreover, EGF-induced RhoA activation was prevented by GEF-H1 silencing, indicating that GEF-H1 is a key downstream effector of the EGFR. The TNF-α-elicited EGFR, ERK, and RhoA stimulation were mediated by the TNF-α convertase enzyme (TACE) that can release EGFR ligands. Further, EGFR transactivation also required the tyrosine kinase Src, as Src inhibition prevented TNF-α-induced activation of the EGFR/ERK/GEF-H1/RhoA pathway. Importantly, a bromodeoxyuridine (BrdU) incorporation assay and electric cell substrate impedance-sensing (ECIS) measurements revealed that TNF-α stimulated cell growth in an EGFR-dependent manner. In contrast, TNF-α-induced NFκB activation was not prevented by EGFR or Src inhibition, suggesting that TNF-α exerts both EGFR-dependent and -independent effects. In summary, in the present study we show that the TNF-α-induced activation of the ERK/GEF-H1/RhoA pathway in tubular cells is mediated through Src- and TACE-dependent EGFR activation. Such a mechanism could couple inflammatory and proliferative stimuli and, thus, may play a key role in the regulation of wound healing and fibrogenesis.
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