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“Signal transduction” refers to the biochemical processes by which cells respond to cues in their internal or external environment. Because signal transduction mechanisms are the natural control circuits that regulate biological systems, they provide potent targets for development of therapeutic agents to combat disease or otherwise alter the behavior of biological systems. Science’s Signal Transduction Knowledge Environment (STKE) is an online resource and information management tool that enables experts and novices in cell signaling to find, organize, and utilize information relevant to processes of cellular regulation. This collection highlights STKE articles and perspectives that provide insight into a variety of signaling pathways.