NDLI: Activin receptor-like kinase 1 modulates transforming growth factor-β1 signaling in the regulation of angiogenesis

Content Provider	PubMed Central
Author	Oh, S. Paul Seki, Tsugio Goss, Kendrick A. Imamura, Takeshi Yi, Youngsuk Donahoe, Patricia K. Li, Li Miyazono, Kohei Dijke, Peter Ten Kim, Seongjin Li, En
Copyright Year	2000
Abstract	The activin receptor-like kinase 1 (ALK1) is a type I receptor for transforming growth factor-β (TGF-β) family proteins. Expression of ALK1 in blood vessels and mutations of the ALK1 gene in human type II hereditary hemorrhagic telangiectasia patients suggest that ALK1 may have an important role during vascular development. To define the function of ALK1 during development, we inactivated the ALK1 gene in mice by gene targeting. The ALK1 homozygous embryos die at midgestation, exhibiting severe vascular abnormalities characterized by excessive fusion of capillary plexes into cavernous vessels and hyperdilation of large vessels. These vascular defects are associated with enhanced expression of angiogenic factors and proteases and are characterized by deficient differentiation and recruitment of vascular smooth muscle cells. The blood vessel defects in ALK1-deficient mice are reminiscent of mice lacking TGF-β1, TGF-β type II receptor (TβR-II), or endoglin, suggesting that ALK1 may mediate TGF-β1 signal in endothelial cells. Consistent with this hypothesis, we demonstrate that ALK1 in endothelial cells binds to TGF-β1 and TβR-II. Furthermore, the ALK1 signaling pathway can inhibit TGF-β1-dependent transcriptional activation mediated by the known TGF-β1 type I receptor, ALK5. Taken together, our results suggest that the balance between the ALK1 and ALK5 signaling pathways in endothelial cells plays a crucial role in determining vascular endothelial properties during angiogenesis.
Starting Page	2626
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	6
Volume Number	97
Language	English
Publisher	The National Academy of Sciences
Publisher Date	2000-03-14
Access Restriction	Open
Rights Holder	The National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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