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Blood, 1 July 2007, Vol. 110, No. 1, pp. 116-124. Prepublished online as a Blood First Edition Paper on March 20, 2007; DOI 10.1182/blood-2006-11-060707. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-11-060707v1 110/1/116    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 Zhang, Y. Articles by Bunting, K. D Search for Related Content PubMed PubMed Citation Articles by Zhang, Y. Articles by Bunting, K. D Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 29, 2006 Accepted March 17, 2007 Abnormal hematopoiesis in Gab2 mutant mice Yi Zhang, Ernesto Diaz-Flores, Geqiang Li, Zhengqi Wang, Zizhen Kang, Eleonora Haviernikova, Sara Rowe, Cheng-Kui Qu, William Tse, Kevin M Shannon, and Kevin D Bunting* Department of Medicine, Division of Hematology/Oncology, Case Western Reserve University, School of Medicine, Cleveland, OH Departments of Pediatrics and Medicine, Program in Developmental and Stem Cell Biology, University of California, San Francisco, CA Case Comprehensive Cancer Center, Cleveland, OH Center for Stem Cell and Regenerative Medicine, Cleveland, OH * Corresponding author; email: kevin.bunting{at}case.edu. Gab2 is an important adapter molecule for cytokine signaling. Despite its major role in signaling by receptors associated with hematopoiesis, the role of Gab2 in hematopoiesis has not been addressed. We report that despite normal numbers of peripheral blood cells, bone marrow cells, and c-Kit+Lin-Sca-1+ (KLS) cells, Gab2-deficient hematopoietic cells are deficient in cytokine responsiveness. Significant reductions in colony-form units in culture (CFU-C) in the presence of limiting cytokine concentrations were observed and these defects could be completely corrected by retroviral complementation. In earlier hematopoiesis, Gab2-deficient KLS cells isolated in vitro responded poorly to hematopoietic growth factors resulting in up to an 11-fold reduction in response to a cocktail of stem cell factor, flt3-ligand, and thrombopoietin. Gab2-deficient c-Kit+Lin- cells also demonstrate impaired activation of ERK and S6 in response to IL-3, which supports defects in activating the phosphatidylinositol-3 kinase and mitogen-associated protein kinase signaling cascades. Associated with the early defects in cytokine response, competitive transplant of Gab2-/- bone marrow cells resulted in defective long-term multilineage repopulation. Therefore, we demonstrate that Gab2 adapter function is intrinsically required for hematopoietic cell response to early-acting cytokines resulting in defective hematopoiesis in Gab2-deficient mice. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Pyarajan, G. Matejovic, J. C. Pratt, S. Baksh, and S. J. Burakoff Interleukin-3 (IL-3)-induced c-fos Activation Is Modulated by Gab2-Calcineurin Interaction J. Biol. Chem., August 29, 2008; 283(35): 23505 - 23509. [Abstract] [Full Text] [PDF]

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