Regulation of ERK Signalling by the Scaffold Protein KSR1

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Mammalian cells contain several signalling pathways that allow them to react to changes in their environment. One of the best-described signalling molecules is the Ras protein, a critical regulator of cellular proliferation, differentiation and survival in multicellular organisms. A major route by which Ras transmits cellular signals is through the sequential activation of the protein kinases Raf-1, MEK and ERK. Activation of this pathway often results in progression through the cell cycle and subsequent cellular proliferation. Because of its central role in growth regulation of mammalian cells, this pathway has to be precisely regulated and defects in its regulation have been attributed to many diseases, including cancer. Scaffold proteins provide spatial and temporal control to cellular signalling by directing associated proteins to specific compartments of the cell. In addition, they physically link several components of a pathway and can exclude others from the complex. In this proposal, we aim to characterise the role of the scaffold protein KSR1 in the regulation of ERK activity after growth factor stimulation of mammalian cells. These studies will provide new insight into the regulation of the ERK signal transduction pathway and will help to understand the processes that cause proliferative diseases like cancer.