Abstract
Activin A receptor like type 1 (ALK1) is a transmembrane serine/threonine receptor kinase in the transforming growth factor-beta receptor family that is expressed on endothelial cells. Defects in ALK1 signaling cause the autosomal dominant vascular disorder, hereditary hemorrhagic telangiectasia (HHT), which is characterized by development of direct connections between arteries and veins, or arteriovenous malformations (AVMs). Although previous studies have implicated ALK1 in various aspects of sprouting angiogenesis, including tip/stalk cell selection, migration, and proliferation, recent work suggests an intriguing role for ALK1 in transducing a flow-based signal that governs directed endothelial cell migration within patent, perfused vessels. In this review, we present an updated view of the mechanism of ALK1 signaling, put forth a unified hypothesis to explain the cellular missteps that lead to AVMs associated with ALK1 deficiency, and discuss emerging roles for ALK1 signaling in diseases beyond HHT.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1-22 |
| Number of pages | 22 |
| Journal | Cellular and Molecular Life Sciences |
| DOIs | |
| State | Accepted/In press - Sep 4 2017 |
| Externally published | Yes |
Keywords
- Activin A receptor like type 1
- Angiogenesis
- Arteriovenous malformation
- Bone morphogenetic protein
- Endoglin
- Hereditary hemorrhagic telangiectasia
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Pharmacology
- Cellular and Molecular Neuroscience
- Cell Biology