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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4093-4101. Prepublished online as a Blood First Edition Paper on February 19, 2004; DOI 10.1182/blood-2003-06-2165. This Article Full Text (PDF) All Versions of this Article: 2003-06-2165v1 103/11/4093    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 Mangan, J. K Articles by Reddy, E P Search for Related Content PubMed PubMed Citation Articles by Mangan, J. K Articles by Reddy, E P Social Bookmarking                   What's this? Submitted June 30, 2003 Accepted February 3, 2004 Mechanisms associated with IL-6-induced upregulation of Jak3 and its role in monocytic differentiation James K Mangan, Sushil G Rane, Anthony D Kang, Arshad Amanullah, Brian C Wong, and E P Reddy* Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA, USA * Corresponding author; email: reddy{at}temple.edu. We report here that Jak3 is a primary response gene for IL-6 in macrophage differentiation and ectopic overexpression of JAK3 accelerates monocytic differentiation of murine M1 myeloid leukemia cells as well as normal mouse bone marrow cells stimulated with cytokines. Furthermore, we show that incubation of normal mouse bone marrow cells with a JAK3-specific inhibitor results in a profound inhibition of myeloid colony formation in response to GM-CSF or the combination of SCF, IL-3, and IL-6. In addition, mutagenesis of the Jak3 promoter has revealed that Sp1 binding sites within a -67 to -85 element and a STAT binding site at position -44 to -53 are critical for activation of Jak3 transcription in M1 cells stimulated with IL-6. EMSA analysis has demonstrated that Sp1 can bind to the -67 to -85 element and STAT3 can bind to the -44 to -53 STAT site in IL-6-stimulated M1 cells. Additionally, ectopic overexpression of STAT3 enhanced Jak3 promoter activity in M1 cells. This mechanism of activation of the murine Jak3 promoter in myeloid cells is distinct from a recently reported method of activation of the human Jak3 promoter in activated T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Joly, C. Lange, M. Thiersch, M. Samardzija, and C. Grimm Leukemia Inhibitory Factor Extends the Lifespan of Injured Photoreceptors In Vivo J. Neurosci., December 17, 2008; 28(51): 13765 - 13774. [Abstract] [Full Text] [PDF] R.-X. Shi, C.-N. Ong, and H.-M. Shen Protein Kinase C Inhibition and X-Linked Inhibitor of Apoptosis Protein Degradation Contribute to the Sensitization Effect of Luteolin on Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis in Cancer Cells Cancer Res., September 1, 2005; 65(17): 7815 - 7823. [Abstract] [Full Text] [PDF]

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