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Blood, 1 February 2004, Vol. 103, No. 3, pp. 912-920. Prepublished online as a Blood First Edition Paper on October 2, 2003; DOI 10.1182/blood-2003-07-2343. This Article Full Text Full Text (PDF) Supplemental Figure and Tables All Versions of this Article: 2003-07-2343v1 103/3/912    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 Haigh, J. J. Articles by Wagner, E. F. Search for Related Content PubMed PubMed Citation Articles by Haigh, J. J. Articles by Wagner, E. F. Related Collections Cell Adhesion and Motility Signal Transduction Hematopoiesis Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Activated Fps/Fes partially rescues the in vivo developmental potential of Flk1-deficient vascular progenitor cells Jody J. Haigh, Masatsugu Ema, Katharina Haigh, Marina Gertsenstein, Peter Greer, Janet Rossant, Andras Nagy, and Erwin F. Wagner From the Mount Sinai Hospital, Samuel Lunenfeld Research Institute, Toronto, Canada; Queen's University Cancer Research Institute, Kingston, Canada; and the Research Institute for Molecular Pathology (IMP), Vienna, Austria. Relatively little is known about the modulators of the vascular endothelial growth factor A (VEGF-A)/Flk1 signaling cascade. To functionally characterize this pathway, VEGF-A stimulation of endothelial cells was performed. VEGF-A–mediated Flk1 activation resulted in increased translocation of the endogenous Fps/Fes cytoplasmic tyrosine kinase to the plasma membrane and increased tyrosine phosphorylation, suggesting a role for Fps/Fes in VEGF-A/Flk1 signaling events. Addition of a myristoylation consensus sequence to Fps/Fes resulted in VEGF-A–independent membrane localization of Fps/Fes in endothelial cells. Expression of the activated Fps/Fes protein in Flk1-deficient embryonic stem (ES) cells rescued their contribution to the developing vascular endothelium in vivo by using ES cell–derived chimeras. Activated Fps/Fes contributed to this rescue event by restoring the migratory potential to Flk1 null progenitors, which is required for movement of hemangioblasts from the primitive streak region into the yolk sac proper. Activated Fps/Fes in the presence of Flk1 increased the number of hemangioblast colonies in vitro and increased the number of mesodermal progenitors in vivo. These results suggest that Fps/Fes may act synergistically with Flk1 to modulate hemangioblast differentiation into the endothelium. We have also demonstrated that activated Fps/Fes causes hemangioma formation in vivo, independently of Flk1, as a result of increasing vascular progenitor density. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Activated Fps/Fes to the rescue Mervin Yoder, Jr Blood 2004 103: 753-754. [Full Text] [PDF] This article has been cited by other articles: P. Religa, R. Cao, M. Bjorndahl, Z. Zhou, Z. Zhu, and Y. Cao Presence of bone marrow-derived circulating progenitor endothelial cells in the newly formed lymphatic vessels Blood, December 15, 2005; 106(13): 4184 - 4190. [Abstract] [Full Text] [PDF]

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