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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1951-1954. Prepublished online as a Blood First Edition Paper on November 10, 2005; DOI 10.1182/blood-2005-05-1834. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-05-1834v1 107/5/1951    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gu, Y. Articles by Chen, Y.-G. Search for Related Content PubMed PubMed Citation Articles by Gu, Y. Articles by Chen, Y.-G. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief report Functional analysis of mutations in the kinase domain of the TGF- receptor ALK1 reveals different mechanisms for induction of hereditary hemorrhagic telangiectasia Yi Gu, Peng Jin, Long Zhang, Xingang Zhao, Xia Gao, Yuanheng Ning, Anming Meng, and Ye-Guang Chen From the State Key Laboratory of Biomembrane and Membrane Biotechnology, the Laboratory of Molecular Cell Biology, the Laboratory of Developmental Biology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China. Genetic studies in mouse and zebrafish have established the importance of activin receptor-like kinase 1 (ALK1) in formation and remodeling of blood vessels. Single-allele mutations in the ALK1 gene have been linked to the human type 2 hereditary hemorrhagic telangiectasia (HHT2). However, how these ALK1 mutations contribute to this disorder remains unclear. To explore the mechanism underlying effect of the HHT-related ALK1 mutations on receptor activity, we generated 11 such mutants and investigated their signaling activities using reporter assay in mammalian cells and examined their effect on zebrafish embryogenesis. Here we show that some of the HHT2-related mutations generate a dominant-negative effect whereas the others give rise to a null phenotype via loss of protein expression or receptor activity. These data indicate that loss-of-function mutations in a single allele of the ALK1 locus are sufficient to contribute to defects in maintaining endothelial integrity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. Twombly, E. Bangi, V. Le, B. Malnic, M. A. Singer, and K. A. Wharton Functional Analysis of saxophone, the Drosophila Gene Encoding the BMP Type I Receptor Ortholog of Human ALK1/ACVRL1 and ACVR1/ALK2 Genetics, October 1, 2009; 183(2): 563 - 579. [Abstract] [Full Text] [PDF] M Shintani, H Yagi, T Nakayama, T Saji, and R Matsuoka A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension J. Med. Genet., May 1, 2009; 46(5): 331 - 337. [Abstract] [Full Text] [PDF]

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