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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2593-2599. Prepublished online as a Blood First Edition Paper on June 26, 2007; DOI 10.1182/blood-2007-02-076471. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-02-076471v1 110/7/2593    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 Voisset, E. Articles by De Sepulveda, P. Search for Related Content PubMed PubMed Citation Articles by Voisset, E. Articles by De Sepulveda, P. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA The tyrosine kinase FES is an essential effector of KITD816V proliferation signal Edwige Voisset1,3, Sophie Lopez1,3, Patrice Dubreuil1,3, and Paulo De Sepulveda1,3 1 Institut National de la Santé et de la Rècherche Médicale (INSERM), Unité Mixte de Recherche (UMR) 599, Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Hématopoïèse Moléculaire et Fonctionnelle, Marseille; 2 Institut Paoli-Calmettes, Marseille; 3 Université de la Méditerranée, Marseille, France KIT is a tyrosine kinase receptor that is aberrantly activated in several neoplasms. In human pathologies, the most frequent mutation of KIT occurs at codon 816. The resulting KIT mutant protein is activated in the absence of ligand and is resistant to the clinically available inhibitors of KIT. In this report, we provide evidence for an essential function of the cytoplasmic tyrosine kinase FES downstream of KITD816V. FES is phosphorylated on tyrosine residues in cells that carry KITD816V mutation, and this phosphorylation is KIT dependent. Reduction of FES expression using RNA interference results in decreased cell proliferation in human or murine cells harboring KITD816V or the homologous mouse mutation KITD814Y. The reduced cell growth can be rescued using another cytokine (granulocyte-macrophage colony-stimulating factor [GM-CSF]) and is not observed when the closely related fer gene is targeted. Finally, signaling downstream of KITD816V is altered in cells lacking FES expression. This study shows a major function of FES downstream of activated KIT receptor and thereby points to FES as a novel target in KIT-related pathologies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Bougherara, F. Subra, R. Crepin, P. Tauc, C. Auclair, and M.-A. Poul The Aberrant Localization of Oncogenic Kit Tyrosine Kinase Receptor Mutants Is Reversed on Specific Inhibitory Treatment Mol. Cancer Res., September 1, 2009; 7(9): 1525 - 1533. [Abstract] [Full Text] [PDF] J. Sun, M. Pedersen, and L. Ronnstrand The D816V Mutation of c-Kit Circumvents a Requirement for Src Family Kinases in c-Kit Signal Transduction J. Biol. Chem., April 24, 2009; 284(17): 11039 - 11047. [Abstract] [Full Text] [PDF]

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