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.