ProteinProtein Interactions in Signaling Cascades

The past decade has seen an explosion in our understanding of the mechamsms underlying the transmission of signals from outside the cell, and the ways in which those signals are interpreted and integrated within the cell. This progress comcides with an appreciation that regulated, stable protein-protein interactions are of central importance to signal transduction (see refs. 1 and 2 ) In the space of a few short years, the way in which we look at these processes has changed in a fundamental way from an emphasis on the regulation of enzymes and their substrate specificities to a new emphasis on the regulation and specificity of protein-binding surfaces. We now appreciate that the cell is less like an aqueous solution in a test tube and more like a dense gel of interacting proteins, where the actual activity of an enzyme is as dependent on its binding partners and subcellular localization as it is on the kinetic parameters of its catalytic activity.