Most physiological processes in cells are regulated by enzymes known as protein kinases. These enzymes act by adding a small negative charge on proteins, a phosphate group. A large fraction of cancers are caused by misregulation of protein kinases.

Discovering the specific functions of kinases in both normal and cancer cells is difficult because kinase inactivation often kills cells. Consistent with this, our understanding of the specific functions of key cell division kinases has been severely limited by our inability to identify mutants – or alternative versions of kinases – with defective enzymatic activity. In order to elucidate the precise roles of protein kinases in cancer, it is necessary to develop novel approaches to control kinase activity in live cells. We have developed a novel way to modulate the activity of protein kinases in living cells. Our main objective in this grant proposal is to use this system to dissect the various molecular functions of the conserved kinases required for cell proliferation.