Analysis of localized PI3K/PTEN signalling

The PI-3 Kinase/PTEN signalling network plays an important role in regulating diverse cellular processes, including cell growth, proliferation, metabolism, cell motility and cell polarity. PI 3-Kinase promotes cell proliferation, growth etc. by catalyzing the phosphorylation of membrane lipid PIP2 (Phosphatidylinositol-4,5-bisphosphate) into PIP3 (Phosphatidylinositol-3,4,5-trisphosphate)and thereby activating various downstream proteins including the AKT kinases. PTEN, a lipid phosphatase, antagonizes PI-3 Kinase by dephosphorylating PIP3 back into PIP2 and acts as a tumor suppressor. Perturbation in this signalling pathway lead to many human cancers. It is frequently assumed that PTEN regulates PI-3 kinase driven cellular responses by reducing the cellular PIP3 pools and thereby inactivating AKT kinases. However, our lab has observed PTEN regulates glioma cell invasion and epithelial cell architecture in an AKT independent manner, the mechanism of which is poorly understood. We hypothesize that PTEN regulates these cellular processes by acting on localized PIP3 pools and through Rac1 mediated pathways. A better understanding of these mechanisms of localized signalling is important in cancer research. This seminar will focus on use of existing techniques and also developing new tools to study the localized PI3K/PTEN signalling in order to understand mechanism by which PTEN regulates glioma cell invasion and epithelial cell architecture.