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

Publisher Website
Google Scholar
Abstract
Transforming growth factor‐β (TGF‐β) 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‐β 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‐β receptor endoglin interact with ALK‐1 (a type I TGF‐β receptor). In addition, endoglin potentiates TGF‐β/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‐β/ALK‐5 signaling. These results suggest that the functional association of endoglin with ALK‐1 is critical for the endothelial responses to TGF‐β.