Figure 5.

Model for the independent regulation of JNK and p38 kinase pathways in the liver. p38 MAP kinase is constitutively active in the liver. Oxidative stress dependent on the pericentral localization of P450 enzymes leads to the activation of JNK and the subsequent phosphorylation of transcription factor substrates such as c-Jun and ATF-2. Furthermore, transcription factors such as JunD are also induced in the pericentral region. Finally, metabolic oxidative stress induces MKP-1 in the pericentral region, perhaps via activation of the JNK signal transduction pathway (30). The induction of MAP kinase phosphatase can suppress the constitutive activity of p38 MAP kinase (9, 22).