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Blood, 1 September 2007, Vol. 110, No. 5, pp. 1420-1428. Prepublished online as a Blood First Edition Paper on May 29, 2007; DOI 10.1182/blood-2007-02-071761. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2007-02-071761v1 110/5/1420    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 Hsu, C.-L. Articles by Kondo, M. Search for Related Content PubMed PubMed Citation Articles by Hsu, C.-L. Articles by Kondo, M. Related Collections Hematopoiesis and Stem Cells Signal Transduction Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS Activation of mitogen-activated protein kinase kinase (MEK)/extracellular signal–regulated kinase (ERK) signaling pathway is involved in myeloid lineage commitment Chia-Lin Hsu1, Kazu Kikuchi1, and Motonari Kondo1 1 Department of Immunology, Duke University Medical Center, Durham, NC Common lymphoid progenitors (CLPs) are lymphoid-lineage-committed progenitor cells. However, they maintain a latent myeloid differentiation potential that can be initiated by stimulation with interleukin-2 (IL-2) via ectopically expressed IL-2 receptors. Although CLPs express IL-7 receptors, which share the common chain with IL-2 receptors, IL-7 cannot initiate lineage conversion in CLPs. In this study, we demonstrate that the critical signals for initiating lineage conversion in CLPs are delivered via IL-2 receptor β (IL-2Rβ) intracellular domains. Fusion of the A region of the IL-2Rβ cytoplasmic tail to IL-7R enables IL-7 to initiate myeloid differentiation in CLPs. We found that Shc, which associates with the A region, mediates lineage conversion signals through the mitogen activated protein kinase (MAPK) pathway. Because mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitors completely blocked IL-2-mediated lineage conversion, MAPK activation, specifically via the MEK/ERK pathway, is critically involved in the initiation of this event. Furthermore, formation of granulocyte/macrophage (GM) colonies by hematopoietic stem cells, but not by common myeloid progenitors (CMPs), was severely reduced in the presence of MEK/ERK inhibitors. These results demonstrate that activation of MEK/ERK plays an important role in GM lineage commitment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Y. Lai, A. Watanabe, T. O'Brien, and M. Kondo Pertussis toxin-sensitive G proteins regulate lymphoid lineage specification in multipotent hematopoietic progenitors Blood, June 4, 2009; 113(23): 5757 - 5764. [Abstract] [Full Text] [PDF] K. Fukushima, I. Matsumura, S. Ezoe, M. Tokunaga, M. Yasumi, Y. Satoh, H. Shibayama, H. Tanaka, A. Iwama, and Y. Kanakura FIP1L1-PDGFR{alpha} Imposes Eosinophil Lineage Commitment on Hematopoietic Stem/Progenitor Cells J. Biol. Chem., March 20, 2009; 284(12): 7719 - 7732. [Abstract] [Full Text] [PDF]

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