Cell Regulation Group - Stress Activated MAP Kinase Pathways & AP-1 Transcription Factor
Cells constantly evaluate and respond to their environment, a process that is key to important biological pathways such as growth control and differentiation. Changes in the environment can lead to promotion of cell growth or induce differentiation. However, changes can often be adverse and sudden, collectively referred to as stress, and it is particularly important that the cells respond to stress in an appropriate manner. Failure to do so can result in the accumulation of damage to DNA that can contribute to cellular ageing to as well as a number of pathogenic conditions including cardiovascular disease and cancer. We are particularly interested in the response to cytotoxic and genotoxic stress which results in the mobilisation of a battery of protective and repair proteins or the induction of apoptosis.
Mitogen-activated protein (MAP) kinase (figure 1) pathways pathways have been identified in all eukaryotic systems, including Drosophila and Yeast. In each case the signalling components include a central core consisting of a serine/threonine kinase (MEKK), a dual specificity kinase (MEK) and a serine/threonine kinase (MAPK). Components of the MAP kinase pathways manage the response to growth stimulatory signals, such as insulin or EGF, as well as adverse signals, such as inflammatory signals, e.g. TNFα, as well as cytotoxic and genotoxic substances and radiation. The latter functions are mainly controlled by stress-activated MAP kinase pathways which consist of members of the JNK and p38 protein kinase families. Important target of these kinases are the AP-1 transcription factors(figure 2) whose functions involve the adaptation to specific external signals through changes in the transcriptional profile of cells.
Figure 1 - MAP Kinase Pathways
Figure 2 - The AP-1 Transcription Factor