Analysis of localized PI3K/PTEN signalling

PI-3 Kinase/PTEN signalling plays an important role in regulating various cellular processes, including cell growth, proliferation, metabolism, cell motility and cell polarity. In cells, PI3-Kinase promotes cell proliferation, growth etc. by catalyzing phosphorylation of membrane lipid PIP2 (Phosphatidylinositol-4,5-bisphosphate) into PIP3 (Phosphatidylinositol-3,4,5-trisphosphate)and thereby activating various downstream effector proteins including AKT kinases. PTEN, a lipid phosphatase, antagonizes PI-3 Kinase by dephosphorylating PIP3 back into PIP2 and acts as a tumor suppressor. Any perturbation in this signalling pathway leads 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 through Rac1 mediated pathway. A better understanding of this mechanism of this 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.