Our group currently focused in two general areas. The first deals with the posttranslational modification and the subcellular localization of cancer signal transduction proteins. The second deals with stress signaling and the characterization of histidine kinases.
Posttranslational modification and subcellular localization of Ras oncogene proteins. It has been known for some time that Ras undergoes posttranslational addition of lipids and this is required for subcellular localization and the signaling functions of Ras. Our interests have included protein prenylation and palmitoylation. Despite extensive characterization of protein prenylation and the development of farnesyltransferase inhibitors (FTIs), many questions remain. For example, it is not known how post-prenylation events influence Ras function. We have recently used a genetic approach, followed by biochemical characterization, to isolate a Ras palmitoyltransferase (PAT). The identification of the Ras PAT provided the handle necessary to identify putative PATs in yeast, flies, worms, mouse, and human. Some of the potential human PAT genes have been linked to human diseases. We plan to pursue studies of protein palmitoylation using a combination of genetics, cell biology, and biochemistry to study yeast and metazoan palmitoylation, with a particular focus on cancer.