Visit our Expo - Redox and Inflammation signaling 2012

SIGNAL TRANSDUCTION BY STRESS-ACTIVATED MAP KINASES
ROGER J. DAVIS
Howard Hughes Medical Institute & University of Massachusetts Medical School,
Worcester, MA 01605 USA, E-mail : Roger.Davis@Umassmed.Edu
The JNK group of stress-activated MAP kinases consists of ten protein kinases that
phosphorylate the NH2-terminal activation domain of c-Jun on Ser-63 and Ser-73 causing
increased transcriptional activity. JNK protein kinase activity is increased in response to
treatment of cells with pro-inflammatory cytokines or exposure to environmental stress.
Activated JNK is phosphorylated on Thr and Tyr within the tripeptide motif Thr-Pro-Tyr
located in kinase sub-domain VIII. Mutational analysis demonstrates that JNK activation
requires the phosphorylation of both Thr and Tyr within this motif. This phosphorylation is
mediated by dual specificity protein kinases, including MKK4 and MKK7.
The function of the JNK signaling pathway has been studied using a combination of
biochemical and genetic approaches. Genetic analysis of JNK signaling in Drosophila
demonstrates that JNK is required for early embryonic morphogenesis. Similarly, disruption
of the JNK signaling pathway in mice using homologous recombination demonstrates that
JNK is required for embryonic viability. In contrast, mice with genetically engineered
selective defects in JNK signaling are viable, but exhibit changes in stress-induced gene
expression and apoptosis. These studies provide insight into the role of the JNK stressactivated
MAP kinase pathway in the cellular response to environmental stress, including
apoptosis and cell survival.
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