REVIEW Cell Signaling in Space and Time: Where Proteins Come Together and When They’re Apart

Signal transduction can be defined as the coordinated relay of messages derived from extracellular cues to intracellular effectors. More simply put, information received on the cell surface is processed across the plasma membrane and transmitted to intracellular targets. This requires that the activators, effectors, enzymes, and substrates that respond to cellular signals come together when they need to. The quest to discover the full complementof cell-signaling components has achievednotable success, and so the next challenge is to establish how these pieces work in concert. In solving this cellular jigsaw puzzle, it is evident that sophisticated regulatory mechanisms ensure that signaling enzymes encounter their intracel-lular substrates in the right place and at the right time. This requires a delicate balance between two apparently opposing processes: the diffusion of information through the cytoplasm and nu-cleus, and the processing of information by im-mobilized multiprotein complexes. Cells have evolved a variety of clever ways to fulfill these requirements: (i) signal-dependent formation of protein complexes; (ii) processing of signals through preassembled multiprotein complexes; (iii) enzyme regulation by subcellular local-ization; and (iv) temporal control of signaling pathways. Here we highlight recent advances in our understanding of these essential regulatory processes