Gene interactions and pathways from curated databases and text-mining
Biochem J 2003, PMID: 12585966

Bidirectional integrin alphaIIbbeta3 signalling regulating platelet adhesion under flow: contribution of protein kinase C.

Giuliano, Simon; Nesbitt, Warwick S; Rooney, Michael; Jackson, Shaun P

Platelet adhesion on von Willebrand factor (vWf) requires the co-ordinated adhesive function of glycoprotein Ib/V/IX and integrin alphaIIbbeta3. Recent evidence [Nesbitt, Kulkarni, Giuliano, Gonclaves, Dopheide, Yap, Harper, Salem and Jackson (2002) J. Biol. Chem. 277, 2965-2972] suggests that outside-in signals from both receptors play important roles in regulating platelet-adhesion dynamics under flow. In the present study, we have examined the mechanisms utilized by protein kinase C (PKC) to promote irreversible platelet adhesion on vWf. We demonstrate that PKC is primarily activated downstream of integrin alphaIIbbeta3, not glycoprotein Ib, during platelet adhesion on vWf. This integrin alphaIIbbeta3-dependent PKC activation establishes a positive-feedback loop that promotes further integrin alphaIIbbeta3 activation, calcium mobilization and firm platelet adhesion. This feedback loop appears to be most relevant at relatively low cytosolic calcium concentrations (mean Delta[Ca(2+)](i);100 nM) as artificially elevating calcium (mean Delta[Ca(2+)](i) > 500 nM) induces integrin alphaIIbbeta3 activation and irreversible platelet adhesion independent of PKC. Our studies demonstrate the existence of a complex signalling relationship operating between PKC, cytosolic calcium and integrin alphaIIbbeta3 that serves to regulate platelet-adhesion dynamics under flow. Furthermore, we have established the existence of PKC-dependent and -independent pathways regulating integrin alphaIIbbeta3 activation and stable platelet adhesion on vWf.

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Text Mining Data

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Manually curated Databases

  • Reactome Reaction: BCAR1 → PTK2 (indirect_complex)
  • Reactome Reaction: BCAR1 → VWF (indirect_complex)
  • Reactome Reaction: FGA → VWF (reaction)
  • Reactome Reaction: BCAR1 → SRC (indirect_complex)
  • Reactome Reaction: RAP1A → RAP1A (reaction)
  • Reactome Reaction: BCAR1 → RAP1A (reaction)
  • Reactome Reaction: FGA → APBB1IP (reaction)
  • Reactome Reaction: FGB → FN1 (reaction)
  • Reactome Reaction: PTK2 → FGB (reaction)
  • Reactome Reaction: ITGB3 → RAP1A (reaction)
  • Reactome Reaction: FGA → SRC (reaction)
  • Reactome Reaction: PTK2 → ITGB3 (reaction)
  • Reactome Reaction: BCAR1 → APBB1IP (indirect_complex)
  • Reactome Reaction: FGG → SRC (reaction)
  • Reactome Reaction: BCAR1 → FN1 (indirect_complex)
  • Reactome Reaction: PTK2 → RAP1A (reaction)
  • Reactome Reaction: ITGB3 → SRC (reaction)
  • Reactome Reaction: ITGB3 → APBB1IP (reaction)
  • Reactome Reaction: BCAR1 → FGG (reaction)
  • Reactome Reaction: RAP1B → APBB1IP (reaction)
  • Reactome Reaction: FGB → VWF (reaction)
  • Reactome Reaction: RAP1B → RAP1B (reaction)
  • Reactome Reaction: FGG → ITGB3 (reaction)
  • Reactome Reaction: FGB → TLN1 (reaction)
  • Reactome Reaction: FGG → RAP1A (reaction)
  • Reactome Reaction: FGB → FGB (reaction)
  • Reactome Reaction: FGA → FN1 (reaction)
  • Reactome Reaction: BCAR1 → FGA (indirect_complex)
  • Reactome Reaction: FGG → VWF (reaction)
  • Reactome Reaction: FGG → RAP1B (reaction)
  • Reactome Reaction: PTK2 → PTK2 (reaction)
  • Reactome Reaction: VWF → APBB1IP (reaction)
  • Reactome Reaction: FGB → RAP1A (reaction)
  • Reactome Reaction: RAP1A → APBB1IP (reaction)
  • Reactome Reaction: TLN1 → TLN1 (reaction)
  • Reactome Reaction: ITGA2B → APBB1IP (reaction)
  • Reactome Reaction: PTK2 → VWF (reaction)
  • Reactome Reaction: PTK2 → ITGA2B (reaction)
  • Reactome Reaction: FGB → ITGB3 (reaction)
  • Reactome Reaction: FGB → FGG (reaction)
  • Reactome Reaction: PTK2 → SRC (reaction)
  • Reactome Reaction: BCAR1 → PTK2 (reaction)
  • Reactome Reaction: SRC → APBB1IP (reaction)
  • Reactome Reaction: RAP1A → RAP1B (reaction)
  • Reactome Reaction: FN1 → ITGA2B (reaction)
  • Reactome Reaction: FGG → FGG (reaction)
  • Reactome Reaction: BCAR1 → ITGA2B (indirect_complex)
  • Reactome Reaction: BCAR1 → FGB (indirect_complex)
  • Reactome Reaction: PTK2 → APBB1IP (reaction)
  • Reactome Reaction: FN1 → SRC (reaction)
  • Reactome Reaction: FGA → FGA (reaction)
  • Reactome Reaction: FGA → FGG (reaction)
  • Reactome Reaction: ITGB3 → RAP1B (reaction)
  • Reactome Reaction: FGG → ITGA2B (reaction)
  • Reactome Reaction: SRC → TLN1 (reaction)
  • Reactome Reaction: ITGA2B → ITGA2B (reaction)
  • Reactome Reaction: RAP1B → TLN1 (reaction)
  • Reactome Reaction: FGA → RAP1A (reaction)
  • Reactome Reaction: PTK2 → FGG (reaction)
  • Reactome Reaction: PTK2 → FGA (reaction)
  • Reactome Reaction: ITGA2B → SRC (reaction)
  • Reactome Reaction: RAP1A → SRC (reaction)
  • Reactome Reaction: FN1 → VWF (reaction)
  • Reactome Reaction: BCAR1 → FGG (indirect_complex)
  • Reactome Reaction: FGG → TLN1 (reaction)
  • Reactome Reaction: VWF → VWF (reaction)
  • Reactome Reaction: BCAR1 → FN1 (reaction)
  • Reactome Reaction: FGA → RAP1B (reaction)
  • Reactome Reaction: FGB → SRC (reaction)
  • Reactome Reaction: FGA → ITGA2B (reaction)
  • Reactome Reaction: BCAR1 → TLN1 (indirect_complex)
  • Reactome Reaction: FGG → FN1 (reaction)
  • Reactome Reaction: BCAR1 → FGB (reaction)
  • Reactome Reaction: RAP1A → TLN1 (reaction)
  • Reactome Reaction: BCAR1 → RAP1B (reaction)
  • Reactome Reaction: RAP1A → VWF (reaction)
  • Reactome Reaction: BCAR1 → TLN1 (reaction)
  • Reactome Reaction: BCAR1 → SRC (reaction)
  • Reactome Reaction: SRC → SRC (reaction)
  • Reactome Reaction: BCAR1 → VWF (reaction)
  • Reactome Reaction: BCAR1 → ITGB3 (indirect_complex)
  • Reactome Reaction: ITGA2B → RAP1A (reaction)
  • Reactome Reaction: SRC → VWF (reaction)
  • Reactome Reaction: ITGA2B → VWF (reaction)
  • Reactome Reaction: FN1 → RAP1B (reaction)
  • Reactome Reaction: FN1 → APBB1IP (reaction)
  • Reactome Reaction: FGA → FGB (reaction)
  • Reactome Reaction: BCAR1 → ITGB3 (reaction)
  • Reactome Reaction: BCAR1 → APBB1IP (reaction)
  • Reactome Reaction: FGG → APBB1IP (reaction)
  • Reactome Reaction: PTK2 → FN1 (reaction)
  • Reactome Reaction: TLN1 → VWF (reaction)
  • Reactome Reaction: BCAR1 → ITGA2B (reaction)
  • Reactome Reaction: ITGB3 → ITGB3 (reaction)
  • Reactome Reaction: FGB → RAP1B (reaction)
  • Reactome Reaction: FGB → ITGA2B (reaction)
  • Reactome Reaction: FN1 → FN1 (reaction)
  • Reactome Reaction: ITGB3 → TLN1 (reaction)
  • Reactome Reaction: FN1 → TLN1 (reaction)
  • Reactome Reaction: PTK2 → TLN1 (reaction)
  • Reactome Reaction: FN1 → RAP1A (reaction)
  • Reactome Reaction: TLN1 → APBB1IP (reaction)
  • Reactome Reaction: BCAR1 → RAP1A (indirect_complex)
  • Reactome Reaction: RAP1B → SRC (reaction)
  • Reactome Reaction: FGA → ITGB3 (reaction)
  • Reactome Reaction: RAP1B → VWF (reaction)
  • Reactome Reaction: BCAR1 → RAP1B (indirect_complex)
  • Reactome Reaction: FGB → APBB1IP (reaction)
  • Reactome Reaction: BCAR1 → FGA (reaction)
  • Reactome Reaction: FN1 → ITGB3 (reaction)
  • Reactome Reaction: PTK2 → RAP1B (reaction)
  • Reactome Reaction: FGA → TLN1 (reaction)
  • Reactome Reaction: ITGA2B → TLN1 (reaction)
  • Reactome Reaction: ITGA2B → ITGB3 (reaction)
  • Reactome Reaction: APBB1IP → APBB1IP (reaction)
  • Reactome Reaction: ITGB3 → VWF (reaction)
  • Reactome Reaction: ITGA2B → RAP1B (reaction)
In total, 104 gene pairs are associated to this article in curated databases