Grant: Operating Grant

The MAP kinases ERK1 and ERK2 are a family of enzymes that play important roles in the control of cell proliferation and differentiation. Accumulating evidence suggests that the ERK1/ERK2 signaling pathway is implicated in the pathogenesis of human diseases including cancer. Inherited mutations in components of this pathway are also associated with a group of developmental disorders causing neurological, cardio-vascular and skeletal anomalies. The objectives of our research program are to understand how the activity of ERK1 and ERK2 MAP kinases is controlled and to define the molecular mechanisms underlying their cellular and physiological actions. We are using a combination of biochemistry, cell biology, proteomics and genetic approaches to address these questions. Specifically, we have generated mouse models in which the genes encoding ERK1 or ERK2 have been inactivated by targeted mutagenesis. These mice are used to study the individual roles of ERK1 and ERK2 and to identify their specific targets. The knowledge gained from our studies should further our understanding of the contribution of ERK1/ERK2 signaling to human diseases and help identify novel and more selective drug targets.