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Blood, 3 September 2009, Vol. 114, No. 10, pp. 2197-2206. Prepublished online as a Blood First Edition Paper on June 8, 2009; DOI 10.1182/blood-2009-01-199166. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2009-01-199166v1 114/10/2197    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 Google Scholar Articles by Shao, E. S. Articles by Boström, K. I. PubMed PubMed Citation Articles by Shao, E. S. Articles by Boström, K. I. Related Collections Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents VASCULAR BIOLOGY Expression of vascular endothelial growth factor is coordinately regulated by the activin-like kinase receptors 1 and 5 in endothelial cells Esther S. Shao1,2, Laura Lin1, Yucheng Yao1, and Kristina I. Boström1,2 1 Division of Cardiology, David Geffen School of Medicine, and 2 Molecular Biology Institute, University of California, Los Angeles Expression of vascular endothelial growth factor (VEGF) is tightly regulated to achieve normal angiogenesis. The objective was to examine regulation of VEGF by the activin-like kinase receptors (ALKs) ALK1 and ALK5. Transforming growth factor β1 (TGFβ1) and bone morphogenetic protein-9 (BMP-9) enhanced and suppressed VEGF expression, respectively, in aortic endothelial cells, as determined by real-time polymerase chain reaction, immunoblotting, cell proliferation, and tube formation. The use of small interfering RNA revealed that TGFβ1 stimulated VEGF expression by activating ALK5, TGFβ type II receptor, and SMAD2, whereas BMP-9 suppressed it by activating ALK1, BMP type II receptor, and SMAD1. ALK1 signaling occurred independently of ALK5 activity. Partial ALK1 deficiency in vitro and in vivo resulted in elevated VEGF expression. In vitro, increased BMP-9 levels normalized VEGF expression in cells with partial, but not severe, ALK1 deficiency. Time course experiments revealed that an increase in ALK1 expression induced by BMP-4, an angiogenic stimulus, preceded induction of ALK5 and VEGF in control cells. In ALK1-deficient cells, however, VEGF expression occurred earlier and was abnormally high, even though ALK5 was not induced. Our results suggest that ALK1 and ALK5 are both essential for correct regulation of VEGF, and that disruption of either pathway leads to disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Bone morphogenetic proteins Dwight A. Towler Blood 2009 114: 2012-2013. [Abstract] [Full Text] [PDF] This article has been cited by other articles: D. A. Towler Bone morphogenetic proteins Blood, September 3, 2009; 114(10): 2012 - 2013. [Abstract] [Full Text] [PDF]

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