Gene interactions and pathways from curated databases and text-mining
EMBO J 2006, PMID: 16810323

FGF-2 protects small cell lung cancer cells from apoptosis through a complex involving PKCepsilon, B-Raf and S6K2.

Pardo, Olivier E; Wellbrock, Claudia; Khanzada, Umme K; Aubert, Muriel; Arozarena, Imanol; Davidson, Sally; Bowen, Frances; Parker, Peter J; Filonenko, V V; Gout, Ivan T; Sebire, Neil; Marais, Richard; Downward, Julian; Seckl, Michael J

Patients with small cell lung cancer (SCLC) die because of chemoresistance. Fibroblast growth factor-2 (FGF-2) increases the expression of antiapoptotic proteins, XIAP and Bcl-X(L), and triggers chemoresistance in SCLC cells. Here we show that these effects are mediated through the formation of a specific multiprotein complex comprising B-Raf, PKCepsilon and S6K2. S6K1, Raf-1 and other PKC isoforms do not form similar complexes. RNAi-mediated downregulation of B-Raf, PKCepsilon or S6K2 abolishes FGF-2-mediated survival. In contrast, overexpression of PKCepsilon increases XIAP and Bcl-X(L) levels and chemoresistance in SCLC cells. In a tetracycline-inducible system, increased S6K2 kinase activity triggers upregulation of XIAP, Bcl-X(L) and prosurvival effects. However, increased S6K1 kinase activity has no such effect. Thus, S6K2 but not S6K1 mediates prosurvival/chemoresistance signalling.

Diseases/Pathways annotated by Medline MESH: Carcinoma, Small Cell, Lung Neoplasms
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Text Mining Data

XIAP → Fibroblast growth factor-2 (FGF-2): " Fibroblast growth factor-2 (FGF-2) increases the expression of antiapoptotic proteins, XIAP and Bcl-X ( L ), and triggers chemoresistance in SCLC cells "

XIAP → S6K2: " In a tetracycline-inducible system, increased S6K2 kinase activity triggers upregulation of XIAP , Bcl-X ( L ) and prosurvival effects "

Manually curated Databases

  • IRef Biogrid Interaction: MAP2K1 — BRAF (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: RPS6KB2 — BRAF (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: RPS6KB2 — BRAF (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RPS6KB2 — PRKCE (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PRKCE — BRAF (physical association, affinity chromatography technology)
  • IRef Hprd Interaction: RPS6 — RPS6KB2 (in vitro)
  • IRef Hprd Interaction: RPS6 — RPS6KB1 (in vitro)
  • IRef Hprd Interaction: MAP2K1 — BRAF (in vivo)
  • IRef Hprd Interaction: MAP2K1 — BRAF (in vitro)
  • IRef Hprd Interaction: PRKCE — MAPK3 (in vivo)
  • IRef Hprd Interaction: PRKCE — RPS6KB2 (in vivo)
  • IRef Hprd Interaction: PRKCE — BRAF (in vivo)
  • IRef Hprd Interaction: Complex of PRKCE-BRAF-PRKCE-BRAF-RPS6KB2-BRAF-PRKCE-RPS6KB2-RPS6KB2 (in vivo)
  • IRef Intact Interaction: RPS6KB2 — RPS6 (phosphorylation reaction, protein kinase assay)
  • IRef Intact Interaction: PRKCA — BRAF (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: RPS6KA2 — PRKCE (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: MAP3K1 — BRAF (phosphorylation reaction, protein kinase assay)
  • IRef Intact Interaction: RPS6KA2 — BRAF (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: RPS6KA2 — RPS6 (phosphorylation reaction, protein kinase assay)
  • IRef Intact Interaction: RPS6KA2 — PRKCA (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: PRKCE — BRAF (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: PRKCE — PRKCA (physical association, anti bait coimmunoprecipitation)
In total, 14 gene pairs are associated to this article in curated databases