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Blood, 19 March 2009, Vol. 113, No. 12, pp. 2706-2714. Prepublished online as a Blood First Edition Paper on December 5, 2008; DOI 10.1182/blood-2008-05-159285. This Article Full Text (PDF) All Versions of this Article: blood-2008-05-159285v1 113/12/2706    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 Benson, D. M Articles by Caligiuri, M. A Search for Related Content PubMed PubMed Citation Articles by Benson, D. M, Jr Articles by Caligiuri, M. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 23, 2008 Accepted November 22, 2008 Stem cell factor and interleukin-2/15 combine to enhance MAPK-mediated proliferation of human natural killer cells Don M Benson Jr, Jianhua Yu, Brian Becknell, Min Wei, Aharon G Freud, Amy K Ferketich, Rossana Trotta, Danilo Perrotti, Roger Briesewitz, and Michael A Caligiuri* Division of Hematology/Oncology, The Ohio State University, Columbus, OH, United States Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH, United States Medical Scientist Program, Integrated Biomedical Graduate Program, College of Medicine, The Ohio State University, Columbus, OH, United States Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, OH, United States Department of Pharmacology, The Ohio State University, Columbus, OH, United States Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States * Corresponding author; email: michael.caligiuri{at}osumc.edu. Stem cell factor (SCF) promotes synergistic cellular proliferation in combination with a number of growth factors, and appears important for normal natural killer (NK) cell development. CD34(+) hematopoietic precursor cells (HPC) require interleukin (IL)-15 for differentiation into human NK cells, and this effect can be mimicked by IL-2. Culture of CD34(+) HPC or some primary human NK cells in IL-2/15 and SCF results in enhanced growth compared with either cytokine alone. The molecular mechanisms responsible for this are unknown and were investigated in the present work. Activation of NK cells by IL-2/15 increases expression of c-kit whose kinase activity is required for synergy with IL-2/15 signaling. Mitogen activated protein kinase (MAPK) signaling intermediaries that are activated both by SCF and IL-2/15 are enhanced in combination to facilitate earlier cell cycle entry. The effect results at least in part via enhanced MAPK-mediated modulation of p27 and CDK4. Collectively the data reveal a novel mechanism by which SCF enhances cellular proliferation in combination with IL-2/15 in primary human NK cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Yu, M. Wei, H. Mao, J. Zhang, T. Hughes, T. Mitsui, I.-k. Park, C. Hwang, S. Liu, G. Marcucci, et al. CD94 Defines Phenotypically and Functionally Distinct Mouse NK Cell Subsets J. Immunol., October 15, 2009; 183(8): 4968 - 4974. [Abstract] [Full Text] [PDF]

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