Protein Phosphorylation Laboratory

Previous and current research
The conversion of environmental cues into cellular actions is effected through a broad class of receptors operating both at the cell surface and intracellularly. These cues range from cell proximal events (e.g. cell-cell, cell-matrix contacts) to distal ones (e.g. systemic hormones) and regulate most aspects of cell functions - metabolism, survival, division, differentiation, migration, etc. Immediately downstream of the receptors that monitor these cues are signal transducers that convert receptor changes into integrated alterations in cellular behaviour. There is abundant evidence that aberrant changes in the properties of such transducers contribute to the uncontrolled growth of transformed cells.

Much of our work has centred upon the way in which these controlling proteins are 'wired up', in particular how the protein kinase C superfamily operates to control cell behaviour and under what circumstances this is misappropriated in cancer. These studies have included definition of signalling networks in which PKCs reside, demonstrating that PKCα confers migratory properties through physical and functional interactions with β1-integrins and ERM proteins and that PKCε confers signal-coupling efficiency to certain receptor classes and the quality of signal output in others, for example having a profound effect on signalling through the c-Met proto-oncogene. Monitoring the cellular environment and responses to a variety of stresses have also been shown to be under the control of members of the PKC-superfamily.

Future projects
Immediate aims are concerned with the signalling pathways operating through different PKC family members to influence stress-induced and migratory responses in cells and in model organisms. We aim to derive a molecular understanding of how these act to determine the physiological and pathological outcomes with a view to developing and exploiting novel therapeutics for intervention in cancer.