Crosstalk between PKCzeta and the IL4/Stat6 pathway during T-cell-mediated 
hepatitis

Duran, A.; Rodriguez, A.; Martin, P.; Serrano, M.; Flores, J. M.; Leitges, M.; Diaz-Meco, M. T.; Moscat, J.

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学術論文

Crosstalk between PKCzeta and the IL4/Stat6 pathway during T-cell-mediated hepatitis

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Leitges, M.
Department of Genes and Behavior, MPI for biophysical chemistry, Max Planck Society;

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引用

Duran, A., Rodriguez, A., Martin, P., Serrano, M., Flores, J. M., Leitges, M., Diaz-Meco, M. T., & Moscat, J. (2004). Crosstalk between PKCzeta and the IL4/Stat6 pathway during T-cell-mediated hepatitis. EMBO Journal, 23(23), 4595-4605. Retrieved from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15526032.

引用: https://hdl.handle.net/11858/00-001M-0000-0012-EBC4-2

要旨

PKCzeta is required for nuclear factor kappa-B (NF-kappaB) activation in several cell systems. NF-kappaB is a suppressor of liver apoptosis during development and in concanavalin A (ConA)-induced T-cell-mediated hepatitis. Here we show that PKCzeta-/- mice display inhibited ConA-induced NF-kappaB activation and reduced damage in liver. As the IL-4/Stat6 pathway is necessary for ConA-induced hepatitis, we addressed here the potential role of PKCzeta in this cascade. Interestingly, the loss of PKCzeta severely attenuated serum IL-5 and liver eotaxin-1 levels, two critical mediators of liver damage. Stat6 tyrosine phosphorylation and Jak1 activation were ablated in the liver of ConA-injected PKCzeta-/- mice and in IL-4-stimulated PKCzeta-/- fibroblasts. PKCzeta interacts with and phosphorylates Jak1 and PKCzeta activity is required for Jak1 function. In contrast, Par-4-/- mice have increased sensitivity to ConA-induced liver damage and IL-4 signaling. This unveils a novel and critical involvement of PKCzeta in the IL-4/Stat6 signaling pathway in vitro and in vivo.