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Blood, 1 March 2007, Vol. 109, No. 5, pp. 1923-1930. Prepublished online as a Blood First Edition Paper on October 12, 2006; DOI 10.1182/blood-2006-06-030841. This Article Full Text (PDF) All Versions of this Article: blood-2006-06-030841v1 109/5/1923    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 Ito, S. Articles by Broxmeyer, H. E. Search for Related Content PubMed PubMed Citation Articles by Ito, S. Articles by Broxmeyer, H. E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 22, 2006 Accepted October 5, 2006 Mad2 is required for optimal hematopoiesis: Mad2 associates with c-Kit in MO7e cells Shigeki Ito, Charlie R Mantel, Myung-Kwan Han, Sunanda Basu, Seiji Fukuda, Scott Cooper, and Hal E. Broxmeyer* Department of Microbiology & Immunology, Indiana University School of Medicine, Indianapolis, IN Department of Microbiology & Immunology, Indiana University, School of Medicine, Indianapolis, IN * Corresponding author; email: hbroxmey{at}iupui.edu. Mitotic arrest deficiency 2 (Mad2) is a component of mitotic spindle checkpoint proteins and essential for accurate chromosome segregation. We investigated a role for Mad2 in hematopoiesis using Mad2 haploinsufficient (Mad2+/-) mice. Mad2+/- bone marrow (BM) and spleen manifested decreased absolute numbers and cycling status of immature, but not mature, hematopoietic progenitor cells. Mad2+/- BM CFU-GM did not manifest synergistic proliferation in response to SCF plus GM-CSF. The percent of annexin V+ cells was higher in Mad2+/- than Mad2+/+ c-Kit+lin- BM after culture with SCF and GM-CSF. However, no significant difference in phosphorylation of extracellular signal-related kinase (Erk1/2) at Thr202/Tyr204 and Akt at Ser473 between Mad2+/- and Mad2+/+ BM c-Kit+lin- cells was observed. Immunoprecipitation assays performed in human MO7e cells demonstrated physical association of c-Kit with Mad2. Moreover, stimulation with SCF plus GM-CSF led to dissociation of Mad2 from c-Kit. Confocal microscopy demonstrated that Mad2 colocalized with c-Kit in the cytoplasm of MO7e cells. These results suggest that Mad2 is involved in synergistic growth of immature hematopoietic progenitor cells in response to SCF plus GM-CSF, effects that may be mediated via physical association of Mad2 with c-Kit. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. A. Markel, M. Wang, P. R. Crisostomo, M. C. Manukyan, J. A. Poynter, and D. R. Meldrum Neonatal stem cells exhibit specific characteristics in function, proliferation, and cellular signaling that distinguish them from their adult counterparts Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2008; 294(5): R1491 - R1497. [Abstract] [Full Text] [PDF]

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