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C/EBP beta serine 64, a phosphoacceptor site, has a critical role in LPS-induced IL-6 and MCP-1 transcription

  1. Author:
    Spooner, C. J.
    Sebastian, T.
    Shuman, J. D.
    Durairaj, S.
    Guo, X. R.
    Johnson, P. F.
    Schwartz, R. C.

  2. Author Address

    Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. NCI, Lab Prot Dynam & Signaling, Ft Detrick, MD 21702 USA. Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA.;Schwartz, RC, Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA.;schwart9@msu.edu
    1. Year: 2007
    2. Date: Feb
  2. Journal: Cytokine
    1. 37
    2. 2
    3. Pages: 119-127
  4. Type of Article: Article
  5. ISSN: 1043-4666
  1. Abstract:

    C/EBPP is a member of the CCAAT/enhancer binding protein family of transcription factors and has been shown to be a critical transcriptional regulator of various proinflammatory genes, including IL-6 and MCP-1. Serine 64 in the transactivation domain of QEHP has recently been identified as a Ras-induced phosphoacceptor site. The integrity of serine 64 along with threonine 189 is important for the Ha-ras (V12)-induced transformation of NIH3T3 cells, however no target genes dependent upon serine 64 for their expression have been reported. In order to evaluate a potential role of serine 64 in C/EBP beta-regulated cytokine expression, we expressed a form of C/EEIP beta with an alanine substitution at serine 64 (C/EBP beta(S64A)) in P388 murine B lymphoblasts, which lack endogenous C/EBP beta expression and are normally unresponsive to LPS for expression of IL-6 and MCP-1. In comparison to wild type C/EBP beta, which robustly supports the LPS-induced expression of IL-6 and MCP-1, C/EBP beta(S64A) was severely impaired in its ability to support the LPS-induced transcription of IL-6 and MCP-1. Furthermore, LPS stimulation increased the level of phosphorylation detected at serine 64. Thus, serine 64, probably through its phospborylation, is a critical determinant of C/EBP beta activity in the transcription of IL-6 and MCP-1. (c) 2007 Elsevier Ltd. All rights reserved.

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  2. DOI: 10.1016/j.cyto.2007.03.001
  3. View record in Web of Science®
  4. WOS: 000246927000003

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