Intracellular signal transduction occurs through cascades of reactions involving dozens of proteins that transmit signals from the cell surface, through a crowded cellular environment filled with organelles and a filamentous cytoskeleton, to specific targets. Numerous signaling molecules are immobilized or transiently bound to the cytoskeleton, yet most models for signaling pathways have no specific role for this mesh, which is often presumed to function primarily as a scaffold that determines cell mechanics but not information flow. We combined analytical tools with several recently established large-scale protein-protein interaction maps for Saccharomyces cerevisiae to quantitatively address the role of the cytoskeleton in intracellular signaling. The results demonstrate that the network of signaling proteins is intimately linked to the cytoskeleton, suggesting that this interconnected filamentous structure plays a crucial and distinct functional role in signal transduction.