Abstract
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.
(c) 2005 Wiley-Liss, Inc.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Activin Receptors, Type I / metabolism*
-
Activin Receptors, Type II
-
Animals
-
Antigens, CD
-
Cell Line
-
Cytoplasm / metabolism
-
Drug Interactions
-
Endoglin
-
Endothelial Cells / metabolism*
-
Extracellular Space / metabolism
-
Gene Expression Regulation
-
Humans
-
Inhibitor of Differentiation Protein 1
-
Promoter Regions, Genetic
-
Protein Serine-Threonine Kinases
-
Protein Structure, Tertiary
-
Receptor, Transforming Growth Factor-beta Type I
-
Receptors, Cell Surface
-
Receptors, Transforming Growth Factor beta / metabolism*
-
Repressor Proteins / genetics
-
Signal Transduction / physiology
-
Transcription Factors / genetics
-
Transfection
-
Vascular Cell Adhesion Molecule-1 / genetics
-
Vascular Cell Adhesion Molecule-1 / metabolism*
Substances
-
Antigens, CD
-
ENG protein, human
-
Endoglin
-
ID1 protein, human
-
Inhibitor of Differentiation Protein 1
-
Receptors, Cell Surface
-
Receptors, Transforming Growth Factor beta
-
Repressor Proteins
-
Transcription Factors
-
Vascular Cell Adhesion Molecule-1
-
Protein Serine-Threonine Kinases
-
ACVRL1 protein, human
-
Activin Receptors, Type I
-
Activin Receptors, Type II
-
Receptor, Transforming Growth Factor-beta Type I
-
TGFBR1 protein, human