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

J Cell Physiol. 2005 Aug;204(2):574-84. doi: 10.1002/jcp.20311.

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.

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