Abstract

The c-Jun N-terminal kinase (JNK) group of mitogen-activated protein kinases (MAP kinases) is activated by exposure of cells to environmental stress and by the treatment of cells with cytokines. The mechanism of activation of JNK is mediated by dual phosphorylation within kinase subdomain VIII on the motif Thr-Pro-Tyr. This phosphorylation is mediated by the MAP kinase kinases MKK4 and MKK7. These MAP kinase kinases serve as signalling molecules that integrate a wide array of stimuli into the activation of the JNK signalling pathway. Studies of the physiological function of JNK have been facilitated by the molecular genetic analysis of JNK signalling in Drosophila and by the creation of mice with targeted disruption of components of the JNK pathway. These studies demonstrate that the JNK pathway regulates AP-1 (activator protein-1) transcriptional activity in vivo and indicate that JNK is required for embryonic morphogenesis, the regulation of cellular proliferation and apoptosis, and the response of cells to immunological stimuli.