Protein kinases and phosphorylation have tended to hog the limelight when it comes to studies on cell signalling. But phosphatases and dephosphorylation are also important in controlling cellular processes. On p. 609, Stuart Kellie and his colleagues fill in some of the gaps in what we know about density-enhanced phosphatase 1 (DEP-1), a receptor-like protein tyrosine phosphatase that is upregulated in epithelial cells as they become confluent. DEP-1 has been implicated in cancer development and in immune cell function but little is known about its function in cells. For their studies, Kellie et al. derived NIH3T3 cell lines in which DEP-1 overexpression could be induced with mifepristone. They show that DEP-1 expression antagonises PDGF receptor signalling and reduces cell proliferation. Noting that DEP-1 expression alters the morphology of the NIH3T3 cells – they round up and become phase bright – the authors also investigated cell-cell and cell-substratum interactions. Overall, they conclude that DEP-1 negatively regulates cell proliferation, cell-substratum contacts, motility and chemotaxis.