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Blood, 1 August 2005, Vol. 106, No. 3, pp. 833-840. Prepublished online as a Blood First Edition Paper on March 22, 2005; DOI 10.1182/blood-2004-11-4458. This Article Full Text Full Text (PDF) Erratum (v106,p2243) All Versions of this Article: 2004-11-4458v1 106/3/833    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kamata, T. Articles by Leavitt, A. D. Search for Related Content PubMed PubMed Citation Articles by Kamata, T. Articles by Leavitt, A. D. Related Collections 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  HEMATOPOIESIS A critical function for B-Raf at multiple stages of myelopoiesis Tamihiro Kamata, Jing Kang, Tzong-Hae Lee, Leszek Wojnowski, Catrin A. Pritchard, and Andrew D. Leavitt From the Department of Laboratory Medicine and Internal Medicine, University of California, San Francisco (UCSF), San Francisco, CA; the Blood Systems Research Institute, San Francisco, CA; the Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany; and the Department of Biochemistry, University of Leicester, Leicester, United Kingdom. Raf kinases play an integral role in the classic mitogen-activated protein (MAP) kinase (Raf/MEK/extracellular signal-related kinase [ERK]) intracellular signaling cascade, but their role in specific developmental processes is largely unknown. Using a genetic approach, we have identified a role for B-Raf during hematopoietic progenitor cell development and during megakaryocytopoiesis. Fetal liver and in vitro embryonic stem (ES) cell–derived myeloid progenitor development is quantitatively impaired in the absence of B-Raf. Biochemical data suggest that this phenotype is due to the loss of a normally occurring rise in B-Raf expression and associated ERK1/2 activation during hematopoietic progenitor cell formation. However, the presence of B-raf–/– ES cell–derived myeloid progenitors in the bone marrow of adult chimeric mice indicates the lack of an obligate cell-autonomous requirement for B-Raf in myeloid progenitor development. The lack of B-Raf also impairs megakaryocytopoiesis. Thrombopoietin (Tpo)–induced in vitro expansion of ES cell–derived megakaryocyte-lineage cells fails to occur in the absence of B-Raf. Moreover, this quantitative in vitro defect in megakaryocyte-lineage expansion is mirrored by chimeric mice data that show reduced B-raf–/– genotype contribution in megakaryocytes relative to its contribution in myeloid progenitors. Together, these data suggest that B-Raf plays a cell-autonomous role in megakaryocytopoiesis and a permissive role in myeloid progenitor development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Unraveling the mysteries of B-Raf: the clot thickens! Philip J. S. Stork Blood 2005 106: 775-776. [Full Text] [PDF]

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