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Blood, 15 March 2008, Vol. 111, No. 6, pp. 3163-3172. Prepublished online as a Blood First Edition Paper on January 8, 2008; DOI 10.1182/blood-2007-09-110510. This Article Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2007-09-110510v1 111/6/3163    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 Monni, R. Articles by Moreau-Gachelin, F. Search for Related Content PubMed PubMed Citation Articles by Monni, R. Articles by Moreau-Gachelin, F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 10, 2007 Accepted December 30, 2007 Ezrin is a target for oncogenic Kit mutants in murine erythroleukemia Richard Monni, Lamya Haddaoui, Alexandra Naba, Isabelle Gallais, Monique Arpin, Patrick Mayeux, and Francoise Moreau-Gachelin* Inserm U830, Paris, France Inserm U567, Paris, France UMR 144 CNRS, Institute Curie, Paris, France Institut Curie, Paris, France Institut Cochin, Universite Descartes, CNRS (UMR 8104), Paris, France * Corresponding author; email: framoreau{at}curie.fr. The model of erythroleukemia caused by Spi-1/PU.1 transgenesis in mice is a multi-stage disease. A preleukemic step is characterized by an acute proliferation of proerythroblasts due to the arrest of differentiation provoked by Spi-1/PU.1. Later on, a blastic crisis occurs associated to somatic oncogenic mutations in the SCF receptor Kit. To gain insights into the mechanisms of the leukemic progression, we performed proteomic profiling analyses of proerythroblasts isolated at the two stages of the disease. Our results indicate that the level of ezrin, a membrane cytoskeletal crosslinker, is increased in the leukemic cells. We showed that Kit oncogenic forms are responsible for ezrin phosphorylation and that phosphorylation rather than overexpression is essential in the leukemic proerythroblasts. Using expression of dominant-negative forms of ezrin, we showed that phosphorylation of ezrin on residue Y353 participates in apoptosis resistance whereas phosphorylation on residue Y145 promotes proliferation of the leukemic cells in vitro and in vivo. Another recurrent oncogenic form of tyrosine kinases (Flt3) most frequently involved in human myeloid leukemia was also able to phosphorylate ezrin. These findings point to a new role for ezrin as signaling player in the development of leukemia, being a downstream effector of oncogenic tyrosine kinases in leukemic blasts. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Austermann, A. R. Nazmi, C. Muller-Tidow, and V. Gerke Characterization of the Ca2+-regulated Ezrin-S100P Interaction and Its Role in Tumor Cell Migration J. Biol. Chem., October 24, 2008; 283(43): 29331 - 29340. [Abstract] [Full Text] [PDF]

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