Targeted disruption of the zetaPKC gene results in the impairment of the NF-kappaB pathway.
Here we have addressed the role that zetaPKC plays in NF-kappaB 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-beta receptor gene-deficient mice. The lack of zetaPKC in embryonic fibroblasts (EFs) severely impairs kappaB-dependent transcriptional activity as well as cytokine-induced phosphorylation of p65. Also, a cytokine-inducible interaction of zetaPKC with p65 was detected which requires the previous degradation of IkappaB. Although in zetaPKC-/- EFs this kinase is not necessary for IKK activation, in lung, which abundantly expresses zetaPKC, IKK activation is inhibited.
Leitges
M
M
Max-Planck-Institut für experimentelle Endokrinologie, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
Sanz
L
L
Martin
P
P
Duran
A
A
Braun
U
U
García
J F
JF
Camacho
F
F
Diaz-Meco
M T
MT
Rennert
P D
PD
Moscat
J
J
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D018390:Gene Targeting; D017930:Genes, Reporter / Q000235:genetics; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D007375:Interleukin-1 / Q000494:pharmacology; D008168:Lung / Q000201:enzymology / Q000502:physiology; D016131:Lymphocyte Subsets / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010581:Peyer's Patches / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D051996:Transcription Factor RelA; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000099221:Protein Kinase C zeta
D000111:Acetylcysteine; D003513:Cycloheximide; D015853:Cysteine Proteinase Inhibitors; D004268:DNA-Binding Proteins; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D007375:Interleukin-1; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011500:Protein Synthesis Inhibitors; D011994:Recombinant Proteins; D051996:Transcription Factor RelA; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000099221:Protein Kinase C zeta; C000606205:Nfkbia protein, mouse; C067713:lactacystin; C496564:Chuk protein, mouse; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse