THE RAS SIGNAL-TRANSDUCTION PATHWAY

Considerable progress has been made over the past year in elucidating the mechanisms by which extracellular signals are transduced via cell surface receptors to trigger changes in gene expression which determine the growth and differentiated state of a cell. In particular, Ras proteins have been implicated as key intermediates that mediate the signal from upstream tyrosine kinases to a downstream cascade of serine/threonine kinases, which then activate nuclear factors that control gene expression and protein synthesis. How Ras proteins function is regulated in this role as a molecular switch, and how the signal is transmitted between the various components of the pathway, are now being determined. Finally, the Rho family of Ras-related proteins, which regulate the actin cytoskeleton, have also been implicated as mediators of oncogenic Ras transformation. The brisk pace at which the key components of Ras-mediated signal transduction pathways are being identified hold great promise that new targets for therapeutic intervention in cancer may now be identified.