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Blood, 15 May 2005, Vol. 105, No. 10, pp. 3935-3938. Prepublished online as a Blood First Edition Paper on February 1, 2005; DOI 10.1182/blood-2004-10-3955. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-10-3955v1 105/10/3935    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 Lelievre, E. Articles by Fong, G.-H. Search for Related Content PubMed PubMed Citation Articles by Lelievre, E. Articles by Fong, G.-H. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Gene Expression Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief report Deficiency in the p110 subunit of PI3K results in diminished Tie2 expression and Tie2-/-–like vascular defects in mice Etienne Lelievre, Pierre-Marie Bourbon, Li-Juan Duan, Robert L. Nussbaum, and Guo-Hua Fong From the Center for Vascular Biology, Departments of Cell Biology and Genetics and Developmental Biology, University of Connecticut Health Center, Farmington; and Genetic Diseases Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD. Phosphoinositide 3-kinase (PI3K) is activated by transmembrane tyrosine kinases such as vascular endothelial growth factor (VEGF) receptors and Tie2 (tunica intima endothelial kinase 2), both of which are key regulators of vascular development. However, the in vivo role of PI3K during developmental vascularization remains to be defined. Here we demonstrate that mice deficient in the p110 catalytic subunit of PI3K display multiple vascular defects, including dilated vessels in the head, reduced branching morphogenesis in the endocardium, lack of hierarchical order of large and small branches in the yolk sac, and impaired development of anterior cardinal veins. These vascular defects are strikingly similar to those in mice defective in the Tie2 signaling pathway. Indeed, Tie2 protein levels were significantly lower in p110-deficient mice. Furthermore, RNA interference of p110 in cultured endothelial cells significantly reduced Tie2 protein levels. These findings raise the possibility that PI3K may function as an upstream regulator of Tie2 expression during mouse development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Brouillard and M. Vikkula Genetic causes of vascular malformations Hum. Mol. Genet., October 15, 2007; 16(R2): R140 - R149. [Abstract] [Full Text] [PDF] J. D. Chang, G. K. Sukhova, P. Libby, E. Schvartz, A. H. Lichtenstein, S. J. Field, C. Kennedy, S. Madhavarapu, J. Luo, D. Wu, et al. Deletion of the phosphoinositide 3-kinase p110{gamma} gene attenuates murine atherosclerosis PNAS, May 8, 2007; 104(19): 8077 - 8082. [Abstract] [Full Text] [PDF] J. K Riley and K. H Moley Glucose utilization and the PI3-K pathway: mechanisms for cell survival in preimplantation embryos. Reproduction, May 1, 2006; 131(5): 823 - 835. [Abstract] [Full Text] [PDF] J. K. Riley, M. O. Carayannopoulos, A. H. Wyman, M. Chi, and K. H. Moley Phosphatidylinositol 3-Kinase Activity Is Critical for Glucose Metabolism and Embryo Survival in Murine Blastocysts J. Biol. Chem., March 3, 2006; 281(9): 6010 - 6019. [Abstract] [Full Text] [PDF]

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