A Novel Protein Kinase C (PKCϵ) Is Required for fMet-Leu-Phe-induced Activation of NF-κB in Human Peripheral Blood Monocytes
| Autor: | Guangming Zhong, Paul F. Lehmann, Zhixing K. Pan, Ling Yu Chen, Shuang Huang, Astrid M. Doerner |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Small interfering RNA
Time Factors RHOA Transcription Genetic Immunoblotting Protein Kinase C-epsilon GTPase Protein Serine-Threonine Kinases Transfection Biochemistry Monocytes chemistry.chemical_compound Humans Immunoprecipitation Protein Isoforms Small GTPase Phosphorylation RNA Small Interfering Luciferases Molecular Biology Protein Kinase C Genes Dominant Inflammation biology Kinase NF-kappa B Chemotaxis NF-κB Cell Biology I-kappa B Kinase Cell biology Enzyme Activation N-Formylmethionine Leucyl-Phenylalanine chemistry biology.protein Signal transduction rhoA GTP-Binding Protein Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 280:22497-22501 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m413033200 |
| Popis: | We have reported that the chemoattractant, fMet-Leu-Phe (fMLP), induces the activation of NF-kappaB in human peripheral blood monocytes and that this requires the activity of small GTPase, RhoA (Huang, S., Chen, L.-Y., Zuraw, B. L., Ye, R. D., and Pan, Z. K. (2001) J. Biol. Chem. 276, 40977-40981). Here we showed that the novel protein kinase C isozyme, PKCepsilon, associates functionally with RhoA in fMLP-stimulated monocytes and that PKCepsilon acted as a signaling component downstream of the GTPase RhoA during fMLP-induced activation of NF-kappaB. Stimulation of monocytes with fMLP resulted in activation of both PKCepsilon and NF-kappaB. This latter activation was largely blocked by specific inhibitors of PKCepsilon by transient expression of a dominant-negative form of PKCepsilon and by PKCepsilon-specific short interfering RNA. These findings demonstrate, for the first time, that fMLP-induced activation of NF-kappaB utilizes a signaling pathway, which requires activity of PKCepsilon, and that PKCepsilon acts as a signaling component downstream of RhoA in cytokine gene transcription stimulated by a chemoattractant. The specificity of this response suggests an important role for the Rho GTPase-PKCepsilon-NF-kappaB pathway in host defense and represents a novel and potentially important mechanism through which fMLP not only attracts leukocytes but may also contribute directly to inflammation. |
| Databáze: | OpenAIRE |
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