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Titolo:
Specificity, diversity, and convergence in VEGF and TNF-alpha signaling events leading to tissue factor up-regulation via EGR-1 in endothelial cells
Autore:
Mechtcheriakova, D; Schabbauer, G; Lucerna, M; Clauss, M; De Martin, R; Binder, BR; Hofer, E;
Indirizzi:
Univ Vienna, VIRCC, Dept Vasc Biol & Thrombosis Res, A-1235 Vienna, Austria Univ Vienna Vienna Austria A-1235 Thrombosis Res, A-1235 Vienna, Austria Max Planck Inst Physiol & Clin Res, Dept Mol Cell Biol, D-61231 Bad Nauheim, Germany Max Planck Inst Physiol & Clin Res Bad Nauheim Germany D-61231, Germany
Titolo Testata:
FASEB JOURNAL
fascicolo: 1, volume: 15, anno: 2001,
pagine: 230 - 242
SICI:
0892-6638(200101)15:1<230:SDACIV>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; TUMOR-NECROSIS-FACTOR; COLONY-STIMULATING FACTOR; RECEPTOR TYROSINE KINASES; GROWTH-FACTOR; MAP KINASE; TRANSCRIPTION FACTOR; NUCLEAR FACTOR; FACTOR GENE;
Keywords:
endothelium; tissue factor; MAP kinases; inflammatory cytokines; angiogenic growth factors;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
74
Recensione:
Indirizzi per estratti:
Indirizzo: Hofer, E Univ Vienna, VIRCC, Dept Vasc Biol & Thrombosis Res, Brunnerstr 59, A-1235Vienna, Austria Univ Vienna Brunnerstr 59 Vienna Austria A-1235 5Vienna, Austria
Citazione:
D. Mechtcheriakova et al., "Specificity, diversity, and convergence in VEGF and TNF-alpha signaling events leading to tissue factor up-regulation via EGR-1 in endothelial cells", FASEB J, 15(1), 2001, pp. 230-242

Abstract

Tissue factor (TF) has been shown to be up-regulated in endothelial cells by the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) as well as by the main angiogenic factor VEGF. Since both stimuli induce the transcription factor EGR-1, which is critically involved in TF gene regulation,we used EGR-1-dependent TF induction as a model to identify potential cross-talks between the various signal transduction cascades initiated by VEGF and TNF-alpha. The data show that at the MAP kinase level, VEGF mainly activates ERK1/2 and p38 MAP kinases in human endothelial cells. TNF-alpha is able to activate all three MAP kinase cascades as well as the classical inflammatory I kappaB/NF kappaB pathway. Furthermore, the MEK-ERK module of MAPkinases appears to act as the convergence point of VEGF- and TNF-alpha -initiated signaling cascades, which lead to the activation of EGR-1 and subsequent TF expression, whereas the upstream signals are distinct. We found that induction of TF by VEGF via EGR-1 is strongly PKC dependent. The TNF-alpha -initiated MEK/ERK cascade connected to EGR-1 and TF expression is clearly less sensitive to PKC inhibition. TNF-ol-mediated activation of MEK/ERK and EGR-1 can be blocked by adenoviral expression of a dominant negative mutant of IKK2, whereas the VEGF signaling pathway is unaffected. Thus, our data demonstrate a new link between the classical inflammatory IKK/I kappaB and the MEK/ERK cascades triggered by TNF-alpha. The additional finding that EGF induces ERK and EGR-1 in a PKC- independent manner and that this signal is not sufficient to up-regulate TF emphasizes the importance of a VEGF-specific signaling pattern for the induction of TF.

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Documento generato il 12/07/20 alle ore 09:36:16