For enzymes, as for house hunters, location can be paramount. That's the conclusion Philippe I. H. Bastiaens of the European Molecular Biology Laboratory and his coworkers have reached in their studies of PTP1B, a signaling enzyme that participates in information transfer within cells by removing a phosphate group from a tyrosine residue on certain receptors (Science 2007, 315, 115). Bastiaens' team reports that PTP1B exists in two forms-one active and the other nearly inactive-in distinct areas of the cell. They suggest that this spatial regulation of PTP1B activity is important for proper maintenance of cellular information transfer. To track enzyme activity in living cells, the team injects cells with a fluorescent version of PTP1B and a dye-tagged peptide substrate containing a protected phosphotyrosine. Only when the protecting group is removed by light irradiation can the substrate bind the active fluorescent enzyme. The researchers mapped energy transfer between the dyes in enzyme-substrate complexes to reveal the distribution of the enzyme's activity in cells.