Signal Transduction by the JNK Group of MAP Kinases

The JNK signal transduction pathway is implicated in many pathological conditions, including cancer. JNK may also mediate cardiac hypertrophic responses, ischemia/reperfusion injury to the heart and kidney, endothelial cell apoptosis caused by diabetes-associated hyperglycemia, and pancreatic beta -cell apoptosis associated with diabetes. JNK has also been implicated in several neurodegenerative diseases. The JNK signaling pathway therefore represents a potential target for therapeutic intervention. A goal for future studies will be to establish whether JNK directly contributes to these disease processes and to define the molecular mechanism of JNK function. A key fundamental question that remains unresolved concerns the ability of cells to interpret JNK activation in different ways depending upon context (e.g., survival signaling versus apoptosis). It is likely that this ability is mediated by interactions of JNK with other signaling pathways within the cell. The combinatorial actions of transcription factors on gene promoters suggests one possible mechanism by which JNK-activated AP-1 could lead to different outcomes in different contexts. In conclusion, progress has been made toward understanding the function of the JNK pathway. Many of the components of this signaling pathway have now been identified. Research during the next few years will be exciting because we will begin to uncover basic molecular mechanisms and gain biological insight into the function of JNK.