Transforming growth factor-beta (TGF-beta) plays an important role in angiogenesis and wound healing. The major cell type involved in angiogenesis are microvascular endothelial cells. Endoglin, a transmembrane glycoprotein, is highly expressed on vascular endothelial cells and has been shown to bind TGF-beta1 and TGF-beta3 and inhibit TGF-beta-induced responses. Mutation in the endoglin gene has been implicated in hereditary haemorrhagic telangiectasia type 1 (HHT1), a dominantly inherited vascular disorder. The role of endoglin in regulating TGF-beta function in the microvasculature is not well understood. The initial interactions on the cell surface between endoglin and the TGF-beta receptors may be an important mechanism by which endoglin modulates TGF-beta signaling and responses. In this study, we show for the first time that on human microvascular endothelial cells, endoglin forms a heteromeric association with betaglycan, a TGF-beta receptor with which endoglin shares limited homology. This complex formation can occur in both a ligand-dependent and ligand-independent manner. In addition, we demonstrate the occurrence of three higher order complexes which contain endoglin and the TGF-beta type II and/or type I receptors in different numbers or ratios. Our results suggest that endoglin may modulate TGF-beta signal transduction by interacting with betaglycan and the TGF-beta signaling receptors on the cell surface in different ratios.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.33041 |
| Date | January 2001 |
| Creators | Wong, Soo Hang, 1971- |
| Contributors | Philip, Anie (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Surgical Research.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001838097, proquestno: MQ75355, Theses scanned by UMI/ProQuest. |
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