| http://purl.uniprot.org/citations/21212278 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21212278 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/21212278 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m110.179903"xsd:string |
| http://purl.uniprot.org/citations/21212278 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
| http://purl.uniprot.org/citations/21212278 | http://purl.uniprot.org/core/author | "Dan Q."xsd:string |
| http://purl.uniprot.org/citations/21212278 | http://purl.uniprot.org/core/author | "Pham M."xsd:string |
| http://purl.uniprot.org/citations/21212278 | http://purl.uniprot.org/core/author | "Szaszi K."xsd:string |
| http://purl.uniprot.org/citations/21212278 | http://purl.uniprot.org/core/author | "Kakiashvili E."xsd:string |
| http://purl.uniprot.org/citations/21212278 | http://purl.uniprot.org/core/author | "Waheed F."xsd:string |
| http://purl.uniprot.org/citations/21212278 | http://purl.uniprot.org/core/author | "Vandermeer M."xsd:string |
| http://purl.uniprot.org/citations/21212278 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21212278 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/21212278 | http://purl.uniprot.org/core/pages | "9268-9279"xsd:string |
| http://purl.uniprot.org/citations/21212278 | http://purl.uniprot.org/core/title | "The epidermal growth factor receptor mediates tumor necrosis factor-alpha-induced activation of the ERK/GEF-H1/RhoA pathway in tubular epithelium."xsd:string |
| http://purl.uniprot.org/citations/21212278 | http://purl.uniprot.org/core/volume | "286"xsd:string |
| http://purl.uniprot.org/citations/21212278 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21212278 |
| http://purl.uniprot.org/citations/21212278 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21212278 |
| http://purl.uniprot.org/uniprot/#_A0A068JD88-mappedCitation-21212278 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21212278 |
| http://purl.uniprot.org/uniprot/#_A8K2T7-mappedCitation-21212278 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21212278 |
| http://purl.uniprot.org/uniprot/#_A0A024R324-mappedCitation-21212278 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21212278 |
| http://purl.uniprot.org/uniprot/#_A0A068JCC9-mappedCitation-21212278 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21212278 |
| http://purl.uniprot.org/uniprot/#_A0A1Y0B9F8-mappedCitation-21212278 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21212278 |
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| http://purl.uniprot.org/uniprot/#_P61586-mappedCitation-21212278 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21212278 |
| http://purl.uniprot.org/uniprot/#_A0A1Y0B9F6-mappedCitation-21212278 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21212278 |