Interaction and functional interplay between endoglin and ALK-1, two components of the endothelial transforming growth factor-β 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 encloglin contributing to this functional cooperation between encloglin and ALK-1. By contrast, encloglin appears to interfere with TGF-beta/ALK-5 signaling. These results suggest that the functional association of encloglin with ALK-1 is critical for the endothelial responses to TGF-beta. J. Cell. Physiol. 204: 574-584, 2005. (c) 2005 Wiley-Liss, Inc.