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http://purl.uniprot.org/citations/22460559http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22460559http://www.w3.org/2000/01/rdf-schema#comment"

Objective

To define the mechanism of p47(phox) phosphorylation in regulating endothelial cell response to tumor necrosis factor-α (TNFα) stimulation.

Methods and results

We replaced 11 serines (303-4, 310, 315, 320, 328, 345, 348, 359, 370, and 379) with alanines and investigated their effects on TNFα (100 U/mL, 30 minutes)-induced acute O(2)(.-) production and mitogen-activated protein kinase phosphorylation in endothelial cells. Seven constructs, S303-4A (double), S310A, S315A, S328A, S345A, S370A, and S379A, significantly reduced the O(2)(.-) production, and 4 of them (S328A, S345A, S370A, and S379A) also inhibited TNFα-induced extracellular-signal-regulated kinase (ERK) 1/2 phosphorylation. Blocking the phosphorylation of S303-4 and S379 inhibited most effectively TNFα-induced O(2)(.-) production. However, phosphorylation of S303-4 was not required for TNFα-induced p47(phox) membrane translocation and binding to TNF receptor-associated factor 4, ERK1/2 activation, and subsequent vascular cell adhesion molecule-1 expression. Knockout of p47(phox) or knockdown of TNF receptor-associated factor 4 using siRNA abolished TNFα-induced ERK1/2 phosphorylation, and inhibition of ERK1/2 activation significantly reduced the TNFα-induced vascular cell adhesion molecule-1 expression.

Conclusions

Phosphorylation of p47(phox) at different serine sites plays distinct roles in endothelial cell response to TNFα stimulation. Double serine (S303-4) phosphorylation is crucial for acute O(2)(.-) production, but is not involved in TNFα signaling through TNF receptor-associated factor 4 and ERK1/2. p47(phox) requires serine phosphorylation at distinct sites to support specific signaling events in response to TNFα."xsd:string
http://purl.uniprot.org/citations/22460559http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.112.247775"xsd:string
http://purl.uniprot.org/citations/22460559http://purl.uniprot.org/core/author"Teng L."xsd:string
http://purl.uniprot.org/citations/22460559http://purl.uniprot.org/core/author"Li J.M."xsd:string
http://purl.uniprot.org/citations/22460559http://purl.uniprot.org/core/author"Fan L.M."xsd:string
http://purl.uniprot.org/citations/22460559http://purl.uniprot.org/core/author"Meijles D."xsd:string
http://purl.uniprot.org/citations/22460559http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22460559http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/22460559http://purl.uniprot.org/core/pages"1488-1496"xsd:string
http://purl.uniprot.org/citations/22460559http://purl.uniprot.org/core/title"Divergent effects of p47(phox) phosphorylation at S303-4 or S379 on tumor necrosis factor-alpha signaling via TRAF4 and MAPK in endothelial cells."xsd:string
http://purl.uniprot.org/citations/22460559http://purl.uniprot.org/core/volume"32"xsd:string
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