Gene interactions and pathways from curated databases and text-mining
Mol Cell Biochem 2003, PMID: 12870650

Phosphoinositide 3-kinase activity leads to silica-induced NF-kappaB activation through interacting with tyrosine-phosphorylated I(kappa)B-alpha and contributing to tyrosine phosphorylation of p65 NF-kappaB.

Kang, Jihee Lee; Lee, Hui Su; Pack, In Soon; Hur, Kyu Chung; Castranova, Vincent

The role of the subunits of phosphoinositide (PI) 3-kinase in NF-kappaB activation in silica-stimulated RAW 264.7 cells was investigated. Results indicate that PI3-kinase activity was increased in response to silica. The p85alpha subunit of PI3-kinase interacted with tyrosine-phosphorylated I(kappa)B-alpha in silica-stimulated cells. PI3-kinase specific inhibitors, such as wortmannin and LY294003, substantially blocked both silica-induced PI3-kinase and NF-kappaB activation. The inhibition of NF-KB activation by PI3-kinase inhibitors was also observed in pervanadate-stimulated but not in LPS-stimulated cells. Furthermore, tyrosine phosphorylation of NF-kappaB p65 was enhanced in cells stimulated with silica, pervanadate or LPS, and wortmannin substantially inhibited the phosphorylation event induced by the first two stimulants but not LPS. Antioxidants, such as superoxide dismutase (SOD), N-acetylcysteine (NAC) and pyrrolidine dithiocarbamate (PDTC), blocked silica-induced PI3-kinase activation, suggesting that reactive oxygen species may be important regulatory molecules in NF-kappaB activation by mediating PI3-kinase activation. Our data suggest that p85 and p110 subunits of PI3-kinase play a role in NF-kappaB activation through interaction with tyrosine-phosphorylated I(kappa)B-alpha and contributing to tyrosine phosphorylation of p65 NF-kappaB.

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Text Mining Data

NF-kappaB → PI3-kinase: " PI3-kinase specific inhibitors, such as wortmannin and LY294003, substantially blocked both silica induced PI3-kinase and NF-kappaB activation "

NF-kappaB → PI3-kinase: " Antioxidants, such as superoxide dismutase ( SOD ), N-acetylcysteine (NAC) and pyrrolidine dithiocarbamate ( PDTC ), blocked silica induced PI3-kinase activation, suggesting that reactive oxygen species may be important regulatory molecules in NF-kappaB activation by mediating PI3-kinase activation "

Manually curated Databases

  • NCI Pathway Database Atypical NF-kappaB pathway: p110-alpha (PIK3CA) → NF kappa B1 p50/RelA complex (NFKB1-RELA) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database Atypical NF-kappaB pathway: p110-alpha (PIK3CA) → I kappa B alpha/PIK3R1 complex (NFKBIA-PIK3R1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database Atypical NF-kappaB pathway: p110-alpha (PIK3CA) → NF kappa B1 p50/RelA/I kappa B alpha complex (NFKB1-NFKBIA-RELA) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database Atypical NF-kappaB pathway: p110-alpha (PIK3CA) → PI3K complex (PIK3CA-PIK3R1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database Atypical NF-kappaB pathway: NF kappa B1 p50/RelA complex (NFKB1-RELA) → I kappa B alpha/PIK3R1 complex (NFKBIA-PIK3R1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database Atypical NF-kappaB pathway: NF kappa B1 p50/RelA complex (NFKB1-RELA) → NF kappa B1 p50/RelA/I kappa B alpha complex (NFKB1-NFKBIA-RELA) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database Atypical NF-kappaB pathway: NF kappa B1 p50/RelA complex (NFKB1-RELA) → PI3K complex (PIK3CA-PIK3R1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database Atypical NF-kappaB pathway: I kappa B alpha/PIK3R1 complex (NFKBIA-PIK3R1) → NF kappa B1 p50/RelA/I kappa B alpha complex (NFKB1-NFKBIA-RELA) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database Atypical NF-kappaB pathway: I kappa B alpha/PIK3R1 complex (NFKBIA-PIK3R1) → PI3K complex (PIK3CA-PIK3R1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database Atypical NF-kappaB pathway: NF kappa B1 p50/RelA/I kappa B alpha complex (NFKB1-NFKBIA-RELA) → PI3K complex (PIK3CA-PIK3R1) (modification, collaborate)
    Evidence: assay, physical interaction
In total, 15 gene pairs are associated to this article in curated databases