J Cell Physiol 2005,
PMID: 15702480
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
Dashed line = No text mining data
Manually curated Databases
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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, -)
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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