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Blood, 1 July 2004, Vol. 104, No. 1, pp. 51-57. Prepublished online as a Blood First Edition Paper on March 2, 2004; DOI 10.1182/blood-2003-07-2554. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2003-07-2554v1 104/1/51    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 Wandzioch, E. Articles by Hallberg, B. Search for Related Content PubMed PubMed Citation Articles by Wandzioch, E. Articles by Hallberg, B. Related Collections Hematopoiesis and Stem Cells Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Activation of the MAP kinase pathway by c-Kit is PI-3 kinase dependent in hematopoietic progenitor/stem cell lines Ewa Wandzioch, Charlotte E. Edling, Ruth H. Palmer, Leif Carlsson, and Bengt Hallberg From the Umeå Center for Molecular Medicine, Umeå Center for Molecular Pathogenesis, and the Department of Medical Biosciences/Pathology, Umeå University, Sweden. The Steel factor (SF) and its receptor c-Kit play a critical role for various cell types at different levels in the hematopoietic hierarchy. Whether similar or distinct signaling pathways are used upon c-Kit activation in different cell types within the hematopoietic hierarchy is not known. To study c-Kit signaling pathways in the hematopoietic system we have compared c-Kit downstream signaling events in SF-dependent hematopoietic stem cell (HSC)–like cell lines to those of mast cells. Both Erk and protein kinase B (PKB)/Akt are activated by ligand-induced activation of the c-Kit receptor in the HSC-like cell lines. Surprisingly, phosphoinositide-3 (PI-3) kinase inhibitors block not only PKB/Akt activation but also activation of Raf and Erk. SF-induced activation of Ras is not affected by inhibition of PI-3 kinase. In mast cells and other more committed hematopoietic precursors, the activation of Erk by SF is not PI-3 kinase dependent. Our results suggest that a molecular signaling switch occurs during differentiation in the hematopoietic system whereby immature hematopoietic progenitor/stem cells use a PI-3 kinase–sensitive pathway in the activation of both Erk and PKB/Akt, which is then switched upon differentiation to the more commonly described PI-3 kinase–independent mitogen-activated protein (MAP) kinase pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Kent, M. Copley, C. Benz, B. Dykstra, M. Bowie, and C. Eaves Regulation of Hematopoietic Stem Cells by the Steel Factor/KIT Signaling Pathway Clin. Cancer Res., April 1, 2008; 14(7): 1926 - 1930. [Abstract] [Full Text] [PDF] C. Sampaio, M. Dance, A. Montagner, T. Edouard, N. Malet, B. Perret, A. Yart, J.-P. Salles, and P. Raynal Signal Strength Dictates Phosphoinositide 3-Kinase Contribution to Ras/Extracellular Signal-Regulated Kinase 1 and 2 Activation via Differential Gab1/Shp2 Recruitment: Consequences for Resistance to Epidermal Growth Factor Receptor Inhibition Mol. Cell. Biol., January 15, 2008; 28(2): 587 - 600. [Abstract] [Full Text] [PDF] L. Armstrong, O. Hughes, S. Yung, L. Hyslop, R. Stewart, I. Wappler, H. Peters, T. Walter, P. Stojkovic, J. Evans, et al. The role of PI3K/AKT, MAPK/ERK and NF{kappa}{beta} signalling in the maintenance of human embryonic stem cell pluripotency and viability highlighted by transcriptional profiling and functional analysis Hum. Mol. Genet., June 1, 2006; 15(11): 1894 - 1913. [Abstract] [Full Text] [PDF] M. F. Tomczak, M. Gadjeva, Y. Y. Wang, K. Brown, I. Maroulakou, P. N. Tsichlis, S. E. Erdman, J. G. Fox, and B. H. Horwitz Defective Activation of ERK in Macrophages Lacking the p50/p105 Subunit of NF-{kappa}B Is Responsible for Elevated Expression of IL-12 p40 Observed after Challenge with Helicobacter hepaticus J. Immunol., January 15, 2006; 176(2): 1244 - 1251. [Abstract] [Full Text] [PDF]

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