Targeted disruption of the zeta PKC gene results in the impairment of the NF-kappa B pathway

Here we have addressed the role that PKC plays in NF-kappaB activation usin g mice in which this kinase was inactivated by homologous recombination. Th ese mice, although grossly normal, showed phenotypic alterations in seconda ry lymphoid organs reminiscent of those of the TNF receptor-1 and of the ly mphotoxin-beta receptor gene-deficient mice. The lack of xi PKC in embryoni c fibroblasts (EFs) severely impairs kappaB-dependent transcriptional activ ity as well as cytokine-induced phosphorylation of p65. Also, a cytokine-in ducible interaction of xi PKC with p65 was detected which requires the prev ious degradation Of I kappaB. Although in xi PKC-/- EFs this kinase is not necessary for IKK activation, in lung, which abundantly expresses xi PKC, I KK activation is inhibited.