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http://purl.uniprot.org/citations/10748004http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10748004http://www.w3.org/2000/01/rdf-schema#comment"Tumor necrosis factor (TNF) and interleukin-1 (IL-1) activate the transcription of both anti-apoptotic and pro-inflammatory gene products in human endothelial cells (EC) via NFkappaB. Here we report that both TNF and IL-1 activate the anti-apoptotic protein kinase Akt in growth factor and serum-deprived EC, assessed by Western blotting for phospho-Akt. Phosphorylation of Akt is blocked by LY294002 or wortmannin, inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase). Consistent with these biochemical observations, TNF and IL-1 reduce apoptosis caused by growth factor and serum deprivation, and this action is also blocked by LY294002. Although Akt has been reported to activate NFkappaB, LY294002 does not prevent TNF- or IL-1-induced degradation of IkappaBalpha, beta, or epsilon, transcription of NFkappaB-dependent E-selectin or ICAM-1 promoter-reporter genes, or surface expression of E-selectin or ICAM-1 in human EC. LY294002 potentiates the activation of mitogen-activated protein kinases and stress-activated protein kinases by TNF and IL-1, suggesting Akt inhibits these responses. We conclude that TNF and IL-1 activate a PI 3-kinase/Akt anti-apoptotic pathway and that the anti-apoptotic effects of Akt are independent of NFkappaB. Moreover, the PI 3-kinase/Akt pathway does not play a major role in the pro-inflammatory responses of EC to TNF or IL-1."xsd:string
http://purl.uniprot.org/citations/10748004http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m001237200"xsd:string
http://purl.uniprot.org/citations/10748004http://purl.uniprot.org/core/author"Pober J.S."xsd:string
http://purl.uniprot.org/citations/10748004http://purl.uniprot.org/core/author"Madge L.A."xsd:string
http://purl.uniprot.org/citations/10748004http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/10748004http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/10748004http://purl.uniprot.org/core/pages"15458-15465"xsd:string
http://purl.uniprot.org/citations/10748004http://purl.uniprot.org/core/title"A phosphatidylinositol 3-kinase/Akt pathway, activated by tumor necrosis factor or interleukin-1, inhibits apoptosis but does not activate NFkappaB in human endothelial cells."xsd:string
http://purl.uniprot.org/citations/10748004http://purl.uniprot.org/core/volume"275"xsd:string
http://purl.uniprot.org/citations/10748004http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/10748004
http://purl.uniprot.org/citations/10748004http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/10748004
http://purl.uniprot.org/uniprot/P31749#attribution-36996F3522BD5AB48CF2611900643CFChttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/10748004
http://purl.uniprot.org/uniprot/P01583#attribution-36996F3522BD5AB48CF2611900643CFChttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/10748004
http://purl.uniprot.org/uniprot/P01584#attribution-A4E63CCA229F840911E8F952A710F047http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/10748004
http://purl.uniprot.org/uniprot/P01375#attribution-82C5B5F1BC1D87BE089EAF059324065Ehttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/10748004
http://purl.uniprot.org/uniprot/P01375#attribution-A4E63CCA229F840911E8F952A710F047http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/10748004