FIBRONECTIN-BINDING PROMOTES A PKC-DEPENDENT MODULATION OF NF-KAPPA-BIN HUMAN T-CELLS

NF-kappa B was identified as one of the transcription factors leading to antigen-independent stimulation through activation of integrin rece ptors. This effect was dependent upon stimulation of alpha(4) beta(1) and alpha(5) beta(1) integrins, the major fibronectin-binding integrin s of Jurkat T cells, since either RGD or CS-1 peptides at 10(-4) M cou ld prevent NF-kappa B activation, At variance with fibroblasts and smo oth 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 p 65 activity. The upregulation of NF-kappa B activity was abrogated by calphostin C, an inhibitor of protein kinase C. Cell adhesion determin ed a strong reduction in the cytoplasmic levels of the NF-kappa B inhi bitor I kappa B alpha, reduction that was prevented after treatment wi th calphostin C, suggesting that PRC-dependent I kappa B alpha phospho rylation might be involved in the upregulation of NF-kappa B. (C) 1998 Academic Press.