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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4536-4544. Prepublished online as a Blood First Edition Paper on February 24, 2004; DOI 10.1182/blood-2003-11-3827. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: 2003-11-3827v1 103/12/4536    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 Zippo, A. Articles by Oliviero, S. Search for Related Content PubMed PubMed Citation Articles by Zippo, A. Articles by Oliviero, S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Gene Expression Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Identification of Flk-1 target genes in vasculogenesis: Pim-1 is required for endothelial and mural cell differentiation in vitro Alessio Zippo, Alessandra De Robertis, Monia Bardelli, Federico Galvagni, and Salvatore Oliviero From the Dipartimento di Biologia Molecolare, Università degli studi di Siena, Siena, Italy. The tyrosine kinase receptor fetal liver kinase 1 (Flk-1) plays a crucial role in vasculogenesis and angiogenesis, but its target genes remain elusive. Comparing Flk-1+/+ with Flk-1-/- embryonic stem (ES) cells, we identified transcripts regulated by the vascular endothelial growth factor A (VEGF-A)/Flk-1 pathway at an early stage of their differentiation to endothelial and mural precursors. Further analysis of a number of these genes (Nm23-M1, Nm23-M2, Slug, Set, pp32, Cbp, Ship-1, Btk, and Pim-1) showed that their products were transiently up-regulated in vivo in endothelial cells (ECs) during angiogenesis of the ovary, and their mRNA was rapidly induced in vitro by VEGF-A in human umbilical cord vein endothelial cells (HUVECs). Functional analysis by RNA interference (RNAi) in ES cells induced to differentiate demonstrated that Pim-1 is required for their differentiation into ECs and smooth muscle cells (SMCs). In HUVECs, RNAi showed that Pim-1 is required in ECs for VEGF-A-dependent proliferation and migration. The identification of Flk-1 target genes should help in elucidating the molecular pathways that govern the vasculogenesis and angiogenesis processes. (Blood. 2004;103:4536-4544) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: VEGF receptors branch into new areas Steven A. Stacker and Marc G. Achen Blood 2004 103: 4379-4380. [Full Text] [PDF] This article has been cited by other articles: J. Chen, M. Kobayashi, S. Darmanin, Y. Qiao, C. Gully, R. Zhao, S. Kondo, H. Wang, H. Wang, S.-C. J. Yeung, et al. Hypoxia-Mediated Up-Regulation of Pim-1 Contributes to Solid Tumor Formation Am. J. Pathol., July 1, 2009; 175(1): 400 - 411. [Abstract] [Full Text] [PDF] K. Tanigaki, C. Mineo, I. S. Yuhanna, K. L. Chambliss, M. J. Quon, E. Bonvini, and P. W. Shaul C-Reactive Protein Inhibits Insulin Activation of Endothelial Nitric Oxide Synthase via the Immunoreceptor Tyrosine-Based Inhibition Motif of Fc{gamma}RIIB and SHIP-1 Circ. 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