Gene interactions and pathways from curated databases and text-mining
J Cell Physiol 2005, PMID: 15702480

Interaction and functional interplay between endoglin and ALK-1, two components of the endothelial transforming growth factor-beta receptor complex.

Blanco, Francisco J; Santibanez, Juan F; Guerrero-Esteo, Mercedes; Langa, Carmen; Vary, Calvin P H; Bernabeu, Carmelo

Transforming growth factor-beta (TGF-beta) signaling in endothelial cells is able to modulate angiogenesis and vascular remodeling, although the underlying molecular mechanisms remain poorly understood. Endoglin and ALK-1 are components of the TGF-beta receptor complex, predominantly expressed in endothelial cells, and mutations in either endoglin or ALK-1 genes are responsible for the vascular dysplasia known as hereditary hemorrhagic telangiectasia. Here we find that the extracellular and cytoplasmic domains of the auxiliary TGF-beta receptor endoglin interact with ALK-1 (a type I TGF-beta receptor). In addition, endoglin potentiates TGF-beta/ALK1 signaling, with the extracellular domain of endoglin contributing to this functional cooperation between endoglin and ALK-1. By contrast, endoglin appears to interfere with TGF-beta/ALK-5 signaling. These results suggest that the functional association of endoglin with ALK-1 is critical for the endothelial responses to TGF-beta.

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Text Mining Data

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Manually curated Databases

  • IRef Biogrid Interaction: ENG — TGFBR2 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: ACVRL1 — ENG (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: TGFBR1 — ENG (physical association, affinity chromatography technology)
  • IRef Innatedb Interaction: ACVRL1 — ENG (unknown, -)
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/CK2B complex (TGFBR2-TGFBR1-ACVRL1-CSNK2B-ENG-TGFB1) → FKBP12 (FKBP1A) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/CK2B complex (TGFBR2-TGFBR1-ACVRL1-CSNK2B-ENG-TGFB1) → CK2B/FKBP12/ALK1 (dimer) complex (FKBP1A-ACVRL1-CSNK2B) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/CK2B complex (TGFBR2-TGFBR1-ACVRL1-CSNK2B-ENG-TGFB1) → FKBP12/TGFBR1 (dimer) complex (TGFBR1-FKBP1A) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/CK2B complex (TGFBR2-TGFBR1-ACVRL1-CSNK2B-ENG-TGFB1) → TGFB1/TGFBR2/Endoglin (dimer) complex (TGFBR2-ENG-TGFB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: FKBP12 (FKBP1A) → CK2B/FKBP12/ALK1 (dimer) complex (FKBP1A-ACVRL1-CSNK2B) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: FKBP12 (FKBP1A) → FKBP12/TGFBR1 (dimer) complex (TGFBR1-FKBP1A) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: FKBP12 (FKBP1A) → TGFB1/TGFBR2/Endoglin (dimer) complex (TGFBR2-ENG-TGFB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: CK2B/FKBP12/ALK1 (dimer) complex (FKBP1A-ACVRL1-CSNK2B) → FKBP12/TGFBR1 (dimer) complex (TGFBR1-FKBP1A) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: CK2B/FKBP12/ALK1 (dimer) complex (FKBP1A-ACVRL1-CSNK2B) → TGFB1/TGFBR2/Endoglin (dimer) complex (TGFBR2-ENG-TGFB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: FKBP12/TGFBR1 (dimer) complex (TGFBR1-FKBP1A) → TGFB1/TGFBR2/Endoglin (dimer) complex (TGFBR2-ENG-TGFB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/CK2B complex (TGFBR2-TGFBR1-ACVRL1-CSNK2B-ENG-TGFB1) → SMAD1-5-8-active (SMAD1/SMAD9/SMAD5) (modification, activates)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/CK2B complex (TGFBR2-TGFBR1-ACVRL1-CSNK2B-ENG-TGFB1) → SMAD1-5-8 (SMAD1/SMAD9/SMAD5) (modification, activates)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database ALK1 signaling events: SMAD1-5-8-active (SMAD1/SMAD9/SMAD5) → SMAD1-5-8 (SMAD1/SMAD9/SMAD5) (modification, collaborate)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/CAV1 complex (TGFBR2-TGFBR1-ACVRL1-CAV1-ENG-TGFB1) → SMAD1-5-8-active (SMAD1/SMAD9/SMAD5) (modification, activates)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/CAV1 complex (TGFBR2-TGFBR1-ACVRL1-CAV1-ENG-TGFB1) → TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/PPP1CA complex (TGFBR2-TGFBR1-ACVRL1-PPP1CA-ENG-TGFB1) (modification, activates)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/CAV1 complex (TGFBR2-TGFBR1-ACVRL1-CAV1-ENG-TGFB1) → SMAD1-5-8 (SMAD1/SMAD9/SMAD5) (modification, activates)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database ALK1 signaling events: SMAD1-5-8-active (SMAD1/SMAD9/SMAD5) → SMAD1-5-8 (SMAD1/SMAD9/SMAD5) (modification, collaborate)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1/PPP1CA complex (TGFBR2-TGFBR1-ACVRL1-PPP1CA-ENG-TGFB1) → SMAD1-5-8 (SMAD1/SMAD9/SMAD5) (modification, inhibits)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1 complex (TGFBR2-TGFBR1-ACVRL1-ENG-TGFB1) → FKBP12 (FKBP1A) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1 complex (TGFBR2-TGFBR1-ACVRL1-ENG-TGFB1) → FKBP12/TGFBR1 (dimer) complex (TGFBR1-FKBP1A) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1 complex (TGFBR2-TGFBR1-ACVRL1-ENG-TGFB1) → FKBP12/ALK1 (dimer) complex (FKBP1A-ACVRL1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: TGFB1/TGFBR2/Endoglin/TGFBR1/ALK1 complex (TGFBR2-TGFBR1-ACVRL1-ENG-TGFB1) → TGFB1/TGFBR2/Endoglin (dimer) complex (TGFBR2-ENG-TGFB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: FKBP12 (FKBP1A) → FKBP12/TGFBR1 (dimer) complex (TGFBR1-FKBP1A) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: FKBP12 (FKBP1A) → FKBP12/ALK1 (dimer) complex (FKBP1A-ACVRL1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: FKBP12 (FKBP1A) → TGFB1/TGFBR2/Endoglin (dimer) complex (TGFBR2-ENG-TGFB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: FKBP12/TGFBR1 (dimer) complex (TGFBR1-FKBP1A) → FKBP12/ALK1 (dimer) complex (FKBP1A-ACVRL1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: FKBP12/TGFBR1 (dimer) complex (TGFBR1-FKBP1A) → TGFB1/TGFBR2/Endoglin (dimer) complex (TGFBR2-ENG-TGFB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database ALK1 signaling events: FKBP12/ALK1 (dimer) complex (FKBP1A-ACVRL1) → TGFB1/TGFBR2/Endoglin (dimer) complex (TGFBR2-ENG-TGFB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
In total, 69 gene pairs are associated to this article in curated databases