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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3106-3113. Prepublished online as a Blood First Edition Paper on December 20, 2005; DOI 10.1182/blood-2005-07-2953. This Article Full Text (PDF) All Versions of this Article: 2005-07-2953v1 107/8/3106    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 Hamelin, V. Articles by Gaudry, M. Search for Related Content PubMed PubMed Citation Articles by Hamelin, V. Articles by Gaudry, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 22, 2005 Accepted December 2, 2005 Thrombopoietin regulates IEX-1 gene expression through ERK-induced AML1 phosphorylation Virginie Hamelin, Claire Letourneux, Paul-Henri Romeo, Francoise Porteu, and Murielle Gaudry* Department Hematologie, Institut Cochin, INSERM U567, Universite Paris Descartes, Faculte de Medecine Rene Descartes, Paris, France * Corresponding author; email: gaudry{at}cochin.inserm.fr. The extra-cellular signal-regulated kinases (ERKs) are required for thrombopoietin (TPO) functions on hematopoietic cells but the ERKs targets involved remain unknown. Here we show that the regulation of the Immediate early gene X-1 (IEX-1), identified as an ERK substrate in response to TPO, was mediated by an ERK-dependent phosphorylation of AML1. The addition of TPO to UT7-Mpl cells and primary megakaryocytes induced gene expression of IEX-1. Neither erythropoietin (EPO) nor granulocyte macrophage-colony stimulating factor (GM-CSF) were able to activate IEX-1 gene expression in UT7-Mpl cells. The induced expression was mediated by a transcriptional activation of the IEX-1 promoter and required an AML1 binding site located at -1068. The direct involvement of AML1 in the regulation of IEX-1 gene expression was shown by both the use of AML1 mutants, and by shRNA experiments targeting endogenous AML1. Finally, the ability of TPO to induce the IEX-1 gene expression was inhibited by U0126, a specific inhibitor of the ERKs activator MEK and AML1 transcriptional activity was shown to be modulated by TPO through ERK-dependent phosphorylation. Taken together, these data suggest that AML1 plays a role in modulating the IEX-1 expression and that the ERK-dependent AML1 phosphorylation regulates the TPO-mediated activation of IEX-1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. P. Steensma, J. D. Neiger, J. C. Porcher, J. J. Keats, P. L. Bergsagel, T. R. Dennis, R. A. Knudson, R. B. Jenkins, R. Santana-Davila, R. Kumar, et al. Rearrangements and Amplification of IER3 (IEX-1) Represent a Novel and Recurrent Molecular Abnormality in Myelodysplastic Syndromes Cancer Res., October 1, 2009; 69(19): 7518 - 7523. [Abstract] [Full Text] [PDF] K. E. Elagib, I. S. Mihaylov, L. L. Delehanty, G. C. Bullock, K. D. Ouma, J. F. Caronia, S. L. Gonias, and A. N. Goldfarb Cross-talk of GATA-1 and P-TEFb in megakaryocyte differentiation Blood, December 15, 2008; 112(13): 4884 - 4894. [Abstract] [Full Text] [PDF] L. Petit-Cocault, C. Volle-Challier, M. Fleury, B. Peault, and M. Souyri Dual role of Mpl receptor during the establishment of definitive hematopoiesis Development, August 15, 2007; 134(16): 3031 - 3040. [Abstract] [Full Text] [PDF] G. Rocher, C. Letourneux, P. Lenormand, and F. Porteu Inhibition of B56-containing Protein Phosphatase 2As by the Early Response Gene IEX-1 Leads to Control of Akt Activity J. Biol. Chem., February 23, 2007; 282(8): 5468 - 5477. [Abstract] [Full Text] [PDF]

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