Oncogenic signaling from the plasma membrane

Abstract

Signaling reactions on membranes play an important role in extracellular information processing by cells. The amount of signaling proteins on the plasma membrane is dynamically maintained by cells to tightly control the qualitative response properties of the signaling system. When oncogenic mutations occur in signaling proteins that are associated with the plasma membrane, the ensemble behavior of signaling molecules can change to a completely different response regime that changes the phenotype of the cell. In order to illuminate the relevance of this spatial dimension in signaling systems, we will first describe how the concentration of signaling proteins determines the qualitative response properties of simple reaction cycles in homogenous protein solutions. From there, we discuss how this concentration parameter is determined by the spatial distribution of proteins in cells and expand this to explain how the translocation of signaling proteins to membrane surfaces elicits a signaling response by changing their local concentration. Within this framework we then describe how an oncogene product's interaction with its wild-type variant can lead to qualitatively different signaling behaviors that depend on their local concentration at membranes as maintained by spatially organizing reactions. We then argue that spatially organizing reaction systems provide an interesting target for cancer therapy.