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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this? Submitted July 10, 2003 Accepted September 11, 2003 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 A Greer, Janet Rossant, Andras Nagy, and Erwin F Wagner Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Research Institute for Molecular Pathology (IMP), Vienna, Austria Cancer Research Institute, Queen's University, Kingston, ON, Canada * Corresponding author; email: haigh{at}mshri.on.ca. Relatively little is known about the modulators of the VEGF-A/Flk1 signalling cascade. To functionally characterize this pathway, VEGF-A stimulation of endothelial cells was performed. VEGFA-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 signalling 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 ES cells rescued their contribution to the developing vascular endothelium in vivo 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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