Interaction and functional interplay between endoglin and ALK-1, two components of the endothelial transforming growth factor-beta receptor complex.
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.
Blanco
Francisco J
FJ
Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas (CSIC), Madrid, Spain.
Santibanez
Juan F
JF
Guerrero-Esteo
Mercedes
M
Langa
Carmen
C
Vary
Calvin P H
CP
Bernabeu
Carmelo
C
D030201:Activin Receptors, Type I / Q000378:metabolism*; D030301:Activin Receptors, Type II; D000818:Animals; D015703:Antigens, CD; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D004347:Drug Interactions; D000071063:Endoglin; D042783:Endothelial Cells / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary; D000077293:Receptor, Transforming Growth Factor-beta Type I; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D012097:Repressor Proteins; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1; D017346:Protein Serine-Threonine Kinases; C425364:ACVRL1 protein, human; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human