[HTML][HTML] Targeted disruption of the ζPKC gene results in the impairment of the NF-κB pathway

M Leitges, L Sanz, P Martin, A Duran, U Braun… - Molecular cell, 2001 - cell.com
M Leitges, L Sanz, P Martin, A Duran, U Braun, JF Garcı́a, F Camacho, MT Diaz-Meco
Molecular cell, 2001cell.com
Here we have addressed the role that ζPKC plays in NF-κB activation using mice in which
this kinase was inactivated by homologous recombination. These mice, although grossly
normal, showed phenotypic alterations in secondary lymphoid organs reminiscent of those
of the TNF receptor-1 and of the lymphotoxin-β receptor gene-deficient mice. The lack of
ζPKC in embryonic fibroblasts (EFs) severely impairs κB-dependent transcriptional activity
as well as cytokine-induced phosphorylation of p65. Also, a cytokine-inducible interaction of …
Abstract
Here we have addressed the role that ζPKC plays in NF-κB activation using mice in which this kinase was inactivated by homologous recombination. These mice, although grossly normal, showed phenotypic alterations in secondary lymphoid organs reminiscent of those of the TNF receptor-1 and of the lymphotoxin-β receptor gene-deficient mice. The lack of ζPKC in embryonic fibroblasts (EFs) severely impairs κB-dependent transcriptional activity as well as cytokine-induced phosphorylation of p65. Also, a cytokine-inducible interaction of ζPKC with p65 was detected which requires the previous degradation of IκB. Although in ζPKC−/− EFs this kinase is not necessary for IKK activation, in lung, which abundantly expresses ζPKC, IKK activation is inhibited.
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