Fibronectin binding promotes a PKC-dependent modulation of NF-kappa B in human T cells.
NF-kappa B was identified as one of the transcription factors leading to antigen-independent stimulation through activation of integrin receptors. This effect was dependent upon stimulation of alpha 4 beta 1 and alpha 5 beta 1 integrins, the major fibronectin-binding integrins of Jurkat T cells, since either RGD or CS-1 peptides at 10(-4) M could prevent NF-kappa B activation. At variance with fibroblasts and smooth muscle cells, in which only p50 and p65 components of the NF-kappa B complex are induced, adhesion of T cells to fibronectin resulted in a strong upregulation of p50 and c-Rel and in a partial increase in p65 activity. The upregulation of NF-kappa B activity was abrogated by calphostin C, an inhibitor of protein kinase C. Cell adhesion determined a strong reduction in the cytoplasmic levels of the NF-kappa B inhibitor I kappa B alpha, reduction that was prevented after treatment with calphostin C, suggesting that PKC-dependent I kappa B alpha phosphorylation might be involved in the upregulation of NF-kappa B.
Bearz
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Department of Biomedical Sciences and Technologies, University of Udine, Italy.
Tell
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Colombatti
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Formisano
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Pucillo
C
C
D001667:Binding, Competitive; D002448:Cell Adhesion; D004268:DNA-Binding Proteins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017469:Receptors, Fibronectin / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005353:Fibronectins; D020672:I-kappa B Proteins; D039041:Integrin alpha4beta1; D016023:Integrins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D009281:Naphthalenes; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing; D000072000:NF-KappaB Inhibitor alpha; D011493:Protein Kinase C; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate