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Blood, 15 May 2005, Vol. 105, No. 10, pp. 3841-3847. Prepublished online as a Blood First Edition Paper on January 27, 2005; DOI 10.1182/blood-2004-09-3708. This Article Full Text (PDF) All Versions of this Article: 2004-09-3708v1 105/10/3841    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 Williamson, E. A Articles by Koeffler, H P Search for Related Content PubMed PubMed Citation Articles by Williamson, E. A Articles by Koeffler, H P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 24, 2004 Accepted January 1, 2005 CCAAT/enhancer binding protein epsilon: changes in function upon phosphorylation by p38 MAP kinase Elizabeth A Williamson*, Ian K Williamson, Alexey M Chumakov, Alan D Friedman, and H P Koeffler Department of Medicine, Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA Department of Oncology/Pediatrics, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA * Corresponding author; email: ewilliamson{at}salud.unm.edu. C/EBP, a member of the CCAAT/enhancer binding protein family, is a transcription factor important in neutrophil differentiation. We have determined that it is phosphorylated on multiple serine and threonine residues, and can be a target for phosphorylation by a number of kinases. We identified a threonine at amino acid 75, part of a consensus MAP kinase site within the transactivation domain of C/EBP, as being phosphorylated only by p38 MAP kinase. Phosphorylation of this residue resulted in enhanced transcriptional activity on a myeloid-specific promoter in in vitro transient transfection reporter assays. We also determined that phosphorylation at Thr75 yielded a protein that was more effective at binding its cognate DNA sequence compared to the wild type non-phosphorylated C/EBP. Stable expression of C/EBPT75A in IL-3-dependent 32Dcl3 did not result in the up-regulation of expression of secondary granule genes compared to wild type C/EBP or C/EBPT75D. Therefore we suggest that C/EBP is a target for p38 MAP kinase activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Doulatov, F. Notta, K. L. Rice, L. Howell, A. Zelent, J. D. Licht, and J. E. Dick PLZF is a regulator of homeostatic and cytokine-induced myeloid development Genes & Dev., September 1, 2009; 23(17): 2076 - 2087. [Abstract] [Full Text] [PDF] M. Rizzi, M. P. Tschan, C. Britschgi, A. Britschgi, B. Hugli, T. J. Grob, N. Leupin, B. U. Mueller, H.-U. Simon, A. Ziemiecki, et al. The death-associated protein kinase 2 is up-regulated during normal myeloid differentiation and enhances neutrophil maturation in myeloid leukemic cells J. Leukoc. Biol., June 1, 2007; 81(6): 1599 - 1608. [Abstract] [Full Text] [PDF] A. F. Gombart, J. Grewal, and H. P. Koeffler ATF4 differentially regulates transcriptional activation of myeloid-specific genes by C/EBP{epsilon} and C/EBP{alpha} J. Leukoc. Biol., June 1, 2007; 81(6): 1535 - 1547. [Abstract] [Full Text] [PDF] A. M. Chumakov, A. Silla, E. A. Williamson, and H. P. Koeffler Modulation of DNA binding properties of CCAAT/enhancer binding protein epsilon by heterodimer formation and interactions with NFkappaB pathway Blood, May 15, 2007; 109(10): 4209 - 4219. [Abstract] [Full Text] [PDF] A. Lennartsson, K. Vidovic, M. B. Pass, J. B. Cowland, and U. Gullberg All-trans retinoic acid-induced expression of bactericidal/permeability-increasing protein (BPI) in human myeloid cells correlates to binding of C/EBP{beta} and C/EBP{epsilon} to the BPI promoter J. Leukoc. Biol., July 1, 2006; 80(1): 196 - 203. [Abstract] [Full Text] [PDF] A. F. Gombart, U. Krug, J. O'Kelly, E. An, V. Vegesna, and H. P. Koeffler Aberrant expression of neutrophil and macrophage-related genes in a murine model for human neutrophil-specific granule deficiency J. Leukoc. Biol., November 1, 2005; 78(5): 1153 - 1165. [Abstract] [Full Text] [PDF]

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