TY - JOUR
T1 - ALK1 signaling in development and disease
T2 - new paradigms
AU - Roman, Beth L.
AU - Hinck, Andrew P.
N1 - Funding Information:
R01HL136566, and by the University of Pittsburgh Vascular Medicine Institute, the Hemophilia Center of Western Pennsylvania, and the Institute for Transfusion Medicine. APH is supported by NIH R01GM58670 and P30CA054174.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
KW - Activin A receptor like type 1
KW - Angiogenesis
KW - Arteriovenous malformation
KW - Bone morphogenetic protein
KW - Endoglin
KW - Hereditary hemorrhagic telangiectasia
UR - http://www.scopus.com/inward/record.url?scp=85028818526&partnerID=8YFLogxK
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U2 - 10.1007/s00018-017-2636-4
DO - 10.1007/s00018-017-2636-4
M3 - Review article
C2 - 28871312
AN - SCOPUS:85028818526
VL - 74
SP - 4539
EP - 4560
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
SN - 1420-682X
IS - 24
ER -