Gene interactions and pathways from curated databases and text-mining
EMBO J 2012, PMID: 22327215

Axl is essential for VEGF-A-dependent activation of PI3K/Akt.

Ruan, Guo-Xiang; Kazlauskas, Andrius

Herein, we report that vascular endothelial growth factor A (VEGF-A) engages the PI3K/Akt pathway by a previously unknown mechanism that involves three tyrosine kinases. Upon VEGF-A-dependent activation of VEGF receptor-2 (VEGFR-2), and subsequent TSAd-mediated activation of Src family kinases (SFKs), SFKs engage the receptor tyrosine kinase Axl via its juxtamembrane domain to trigger ligand-independent autophosphorylation at a pair of YXXM motifs that promotes association with PI3K and activation of Akt. Other VEGF-A-mediated signalling pathways are independent of Axl. Interfering with Axl expression or function impairs VEGF-A- but not bFGF-dependent migration of endothelial cells. Similarly, Axl null mice respond poorly to VEGF-A-induced vascular permeability or angiogenesis, whereas other agonists induce a normal response. These results elucidate the mechanism by which VEGF-A activates PI3K/Akt, and identify previously unappreciated potential therapeutic targets of VEGF-A-driven processes.

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Text Mining Data

PI3K/Akt → VEGF-A: " Axl is essential for VEGF-A dependent activation of PI3K/Akt "

PI3K/Akt → Axl: " Axl is essential for VEGF-A dependent activation of PI3K/Akt "

PI3K/Akt → VEGF-A: " Axl is essential for VEGF-A dependent activation of PI3K/Akt "

PI3K/Akt → Axl: " Axl is essential for VEGF-A dependent activation of PI3K/Akt "

Src family kinases (SFKs) → VEGF-A: " Upon VEGF-A dependent activation of VEGF receptor-2 (VEGFR-2), and subsequent TSAd mediated activation of Src family kinases (SFKs) , SFKs engage the receptor tyrosine kinase Axl via its juxtamembrane domain to trigger ligand independent autophosphorylation at a pair of YXXM motifs that promotes association with PI3K and activation of Akt "

Src family kinases (SFKs) → (VEGFR-2): " Upon VEGF-A dependent activation of VEGF receptor-2 (VEGFR-2) , and subsequent TSAd mediated activation of Src family kinases (SFKs) , SFKs engage the receptor tyrosine kinase Axl via its juxtamembrane domain to trigger ligand independent autophosphorylation at a pair of YXXM motifs that promotes association with PI3K and activation of Akt "

(VEGFR-2) → VEGF-A: " Upon VEGF-A dependent activation of VEGF receptor-2 (VEGFR-2) , and subsequent TSAd mediated activation of Src family kinases (SFKs), SFKs engage the receptor tyrosine kinase Axl via its juxtamembrane domain to trigger ligand independent autophosphorylation at a pair of YXXM motifs that promotes association with PI3K and activation of Akt "

PI3K/Akt → VEGF-A: " These results elucidate the mechanism by which VEGF-A activates PI3K/Akt , and identify previously unappreciated potential therapeutic targets of VEGF-A-driven processes "

PI3K/Akt → VEGF-A: " These results elucidate the mechanism by which VEGF-A activates PI3K/Akt , and identify previously unappreciated potential therapeutic targets of VEGF-A-driven processes "

Manually curated Databases

  • IRef Intact Interaction: SRC — AXL (physical association, anti bait coimmunoprecipitation)
  • Reactome Reaction: PIK3CA → SRC (indirect_complex)
  • Reactome Reaction: PIK3R1 → AXL (reaction)
  • Reactome Reaction: PIK3CA → KDR (reaction)
  • Reactome Reaction: PIK3R1 → KDR (reaction)
  • Reactome Reaction: PIK3R1 → SH2D2A (reaction)
  • Reactome Reaction: PIK3R1 → VEGFA (reaction)
  • Reactome Reaction: SH2D2A → VEGFA (reaction)
  • Reactome Reaction: AXL → KDR (reaction)
  • Reactome Reaction: PIK3R2 → AXL (reaction)
  • Reactome Reaction: PIK3R2 → AXL (indirect_complex)
  • Reactome Reaction: PIK3CA → AXL (reaction)
  • Reactome Reaction: PIK3R1 → KDR (indirect_complex)
  • Reactome Reaction: PIK3R2 → SRC (indirect_complex)
  • Reactome Reaction: SH2D2A → KDR (reaction)
  • Reactome Reaction: SRC → KDR (reaction)
  • Reactome Reaction: PIK3CB → SH2D2A (reaction)
  • Reactome Reaction: PIK3CA → AXL (indirect_complex)
  • Reactome Reaction: KDR → KDR (reaction)
  • Reactome Reaction: SH2D2A → SH2D2A (reaction)
  • Reactome Reaction: PIK3R1 → SRC (indirect_complex)
  • Reactome Reaction: PIK3CB → AXL (indirect_complex)
  • Reactome Reaction: AXL → AXL (reaction)
  • Reactome Reaction: SRC → VEGFA (reaction)
  • Reactome Reaction: PIK3R2 → SRC (reaction)
  • Reactome Reaction: PIK3R1 → SH2D2A (indirect_complex)
  • Reactome Reaction: PIK3CA → SH2D2A (reaction)
  • Reactome Reaction: PIK3R2 → KDR (reaction)
  • Reactome Reaction: AXL → KDR (indirect_complex)
  • Reactome Reaction: PIK3CB → VEGFA (indirect_complex)
  • Reactome Reaction: SH2D2A → AXL (indirect_complex)
  • Reactome Reaction: PIK3R1 → AXL (indirect_complex)
  • Reactome Reaction: PIK3CA → VEGFA (indirect_complex)
  • Reactome Reaction: PIK3R2 → SH2D2A (indirect_complex)
  • Reactome Reaction: PIK3CB → VEGFA (reaction)
  • Reactome Reaction: SH2D2A → SRC (reaction)
  • Reactome Reaction: PIK3CB → AXL (reaction)
  • Reactome Reaction: PIK3CB → KDR (indirect_complex)
  • Reactome Reaction: PIK3CA → VEGFA (reaction)
  • Reactome Reaction: PIK3R2 → KDR (indirect_complex)
  • Reactome Reaction: SH2D2A → AXL (reaction)
  • Reactome Reaction: AXL → VEGFA (reaction)
  • Reactome Reaction: KDR → VEGFA (reaction)
  • Reactome Reaction: SRC → SRC (reaction)
  • Reactome Reaction: SRC → AXL (indirect_complex)
  • Reactome Reaction: PIK3CA → KDR (indirect_complex)
  • Reactome Reaction: PIK3R2 → VEGFA (reaction)
  • Reactome Reaction: VEGFA → VEGFA (reaction)
  • Reactome Reaction: PIK3CA → SH2D2A (indirect_complex)
  • Reactome Reaction: PIK3CB → SRC (indirect_complex)
  • Reactome Reaction: SRC → AXL (reaction)
  • Reactome Reaction: PIK3CB → SRC (reaction)
  • Reactome Reaction: PIK3R2 → SH2D2A (reaction)
  • Reactome Reaction: PIK3CB → KDR (reaction)
  • Reactome Reaction: PIK3CA → SRC (reaction)
  • Reactome Reaction: PIK3CB → SH2D2A (indirect_complex)
  • Reactome Reaction: PIK3R1 → VEGFA (indirect_complex)
  • Reactome Reaction: PIK3R2 → VEGFA (indirect_complex)
  • Reactome Reaction: PIK3R1 → SRC (reaction)
  • Reactome Reaction: AXL → VEGFA (indirect_complex)
In total, 35 gene pairs are associated to this article in curated databases