C/EBPbeta serine 64, a phosphoacceptor site, has a critical role in LPS-induced IL-6 and MCP-1 transcription
| Autor: | Richard C. Schwartz, Srinivasan Durairaj, Thomas Sebastian, Chauncey J. Spooner, Peter F. Johnson, Xiangrong Guo, Jon Shuman |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Lipopolysaccharides
Transcription Genetic Immunology Biology Biochemistry Cell Line Serine Transactivation Mice Genes Reporter Enhancer binding Immunology and Allergy Animals Phosphorylation Promoter Regions Genetic Molecular Biology Transcription factor Chemokine CCL2 Serine/threonine-specific protein kinase Ccaat-enhancer-binding proteins Interleukin-6 CCAAT-Enhancer-Binding Protein-beta Wild type Hematology Molecular biology biological phenomena cell phenomena and immunity hormones hormone substitutes and hormone antagonists |
| Zdroj: | Cytokine. 37(2) |
| ISSN: | 1043-4666 |
| Popis: | C/EBPbeta 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 C/EBPbeta 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/EBPbeta-regulated cytokine expression, we expressed a form of C/EBPbeta with an alanine substitution at serine 64 (C/EBPbeta(S64A)) in P388 murine B lymphoblasts, which lack endogenous C/EBPbeta expression and are normally unresponsive to LPS for expression of IL-6 and MCP-1. In comparison to wild type C/EBPbeta, which robustly supports the LPS-induced expression of IL-6 and MCP-1, C/EBPbeta(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 phosphorylation, is a critical determinant of C/EBPbeta activity in the transcription of IL-6 and MCP-1. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect