| First Author | Durán A | Year | 2004 |
| Journal | EMBO J | Volume | 23 |
| Issue | 23 | Pages | 4595-605 |
| PubMed ID | 15526032 | Mgi Jnum | J:115464 |
| Mgi Id | MGI:3691743 | Doi | 10.1038/sj.emboj.7600468 |
| Citation | Duran A, et al. (2004) Crosstalk between PKCzeta and the IL4/Stat6 pathway during T-cell-mediated hepatitis. EMBO J 23(23):4595-605 |
| abstractText | 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. |
