Spatial Organization of Oncogenic Ras on Supported Membranes

Abstract

Ras is a membrane protein which acts as a molecular switch in the activation of many signal transduction pathways involved in cellular processes such as proliferation and apoptosis. Ras has been a subject of great interest due to the causal role found between its hyperactivity and cancer, and studies have shown that approximately 30% of all human cancers have oncogenic Ras mutations. Although Ras has been studied for more than thirty years, the spatial organization of oncogenic Ras on membranes is still not well characterized. It has been suggested that Ras may organize into clusters in cell membranes but the molecular scale structure of these organizations remain unknown. Molecular dimerization of Ras has also been suggested and we quantitatively characterize this in an array of Ras mutants in supported lipid bilayer membranes using fluorescence correlation spectroscopy (FCS) and photon counting histogram analysis (PCH). The implications of Ras clustering on downstream signaling will be discussed.