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Blood, 15 December 2004, Vol. 104, No. 13, pp. 3901-3910. Prepublished online as a Blood First Edition Paper on August 31, 2004; DOI 10.1182/blood-2003-12-4396. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2003-12-4396v1 104/13/3901    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 Harder, K. W. Articles by Hibbs, M. L. Search for Related Content PubMed PubMed Citation Articles by Harder, K. W. Articles by Hibbs, M. L. Related Collections Signal Transduction Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Perturbed myelo/erythropoiesis in Lyn-deficient mice is similar to that in mice lacking the inhibitory phosphatases SHP-1 and SHIP-1 Kenneth W. Harder, Cathy Quilici, Edwina Naik, Melissa Inglese, Nicole Kountouri, Amanda Turner, Kristina Zlatic, David M. Tarlinton, and Margaret L. Hibbs From the Ludwig Institute for Cancer Research, The Royal Melbourne Hospital, Victoria, Australia; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; and the Cooperative Research Centre for Cellular Growth Factors, Melbourne, Australia. The Lyn tyrosine kinase plays essential inhibitory signaling roles within hematopoietic cells by recruiting inhibitory phosphatases such as SH2-domain containing phosphatase-1 (SHP-1), SHP-2, and SH2-domain containing 5'-inositol phosphatase (SHIP-1) to the plasma membrane in response to specific stimuli. Lyn-deficient mice display a collection of hematopoietic defects, including autoimmune disease as a result of autoantibody production, and perturbations in myelopoiesis that ultimately lead to splenomegaly and myeloid neoplasia. In this study, we demonstrate that loss of Lyn results in a stem/progenitor cell-intrinsic defect leading to an age-dependent increase in myeloid, erythroid, and primitive hematopoietic progenitor numbers that is independent of autoimmune disease. Despite possessing increased numbers of erythroid progenitors, and a more robust expansion of these cells following phenylhydrazine challenge, Lyn-deficient mice are more severely affected by the chemotherapeutic drug 5-fluorouracil, revealing a greater proportion of cycling progenitors. We also show that mice lacking SHIP-1 have defects in the erythroid and myeloid compartments similar to those in mice lacking Lyn or SHP-1, suggesting an intimate relationship between Lyn, SHP-1, and SHIP-1 in regulating hematopoiesis. (Blood. 2004;104:3901-3910) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Kannan, A. Audet, H. Huang, L.-j. Chen, and M. Wu Cholesterol-Rich Membrane Rafts and Lyn Are Involved in Phagocytosis during Pseudomonas aeruginosa Infection J. Immunol., February 15, 2008; 180(4): 2396 - 2408. [Abstract] [Full Text] [PDF] H. S. Ramshaw, M. A. Guthridge, F. C. Stomski, E. F. Barry, L. Ooms, C. A. Mitchell, C. G. Begley, and A. F. Lopez The Shc-binding site of the {beta}c subunit of the GM-CSF/IL-3/IL-5 receptors is a negative regulator of hematopoiesis Blood, November 15, 2007; 110(10): 3582 - 3590. [Abstract] [Full Text] [PDF] E. Ingley, J. R. Schneider, C. J. Payne, D. J. McCarthy, K. W. Harder, M. L. Hibbs, and S. P. Klinken Csk-binding Protein Mediates Sequential Enzymatic Down-regulation and Degradation of Lyn in Erythropoietin-stimulated Cells J. Biol. Chem., October 20, 2006; 281(42): 31920 - 31929. [Abstract] [Full Text] [PDF] C. H. Mermel, M. L. McLemore, F. Liu, S. Pereira, J. Woloszynek, C. A. Lowell, and D. C. Link Src family kinases are important negative regulators of G-CSF-dependent granulopoiesis Blood, October 15, 2006; 108(8): 2562 - 2568. [Abstract] [Full Text] [PDF] V. G. Karur, C. A. Lowell, P. Besmer, V. Agosti, and D. M. Wojchowski Lyn kinase promotes erythroblast expansion and late-stage development Blood, September 1, 2006; 108(5): 1524 - 1532. [Abstract] [Full Text] [PDF] Y. Liu, R. Pop, C. Sadegh, C. Brugnara, V. H. Haase, and M. Socolovsky Suppression of Fas-FasL coexpression by erythropoietin mediates erythroblast expansion during the erythropoietic stress response in vivo Blood, July 1, 2006; 108(1): 123 - 133. [Abstract] [Full Text] [PDF] A. Verbrugge, T. de Ruiter, C. Geest, P. J. Coffer, and L. Meyaard Differential expression of leukocyte-associated Ig-like receptor-1 during neutrophil differentiation and activation J. Leukoc. Biol., April 1, 2006; 79(4): 828 - 836. [Abstract] [Full Text] [PDF] M. Muthukuru and C. W. Cutler Upregulation of Immunoregulatory Src Homology 2 Molecule Containing Inositol Phosphatase and Mononuclear Cell Hyporesponsiveness in Oral Mucosa during Chronic Periodontitis Infect. Immun., February 1, 2006; 74(2): 1431 - 1435. [Abstract] [Full Text] [PDF] F. Martelli, B. Ghinassi, B. Panetta, E. Alfani, V. Gatta, A. Pancrazzi, C. Bogani, A. M. Vannucchi, F. Paoletti, G. Migliaccio, et al. Variegation of the phenotype induced by the Gata1low mutation in mice of different genetic backgrounds Blood, December 15, 2005; 106(13): 4102 - 4113. [Abstract] [Full Text] [PDF] S.-J. E. Beavitt, K. W. Harder, J. M. Kemp, J. Jones, C. Quilici, F. Casagranda, E. Lam, D. Turner, S. Brennan, P. D. Sly, et al. Lyn-Deficient Mice Develop Severe, Persistent Asthma: Lyn Is a Critical Negative Regulator of Th2 Immunity J. Immunol., August 1, 2005; 175(3): 1867 - 1875. [Abstract] [Full Text] [PDF]

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