The role of phosphatases in signal transduction.

The importance of phosphatases in regulating the phosphorylation of proteins involved in cell signaling has been demonstrated by four recent discoveries. First, a new family of receptor-like transmembrane phosphotyrosine phosphatases, highly conserved throughout evolution, was shown to be distributed in a wide variety of tissues. Extensive heterogeneity in the extracellular regions of these molecules points to the existence of a wide diversity of ligands. These ligands are thought to mediate transduction of signals to the cell interior by means of the phosphatase activity occurring within the cytoplasmic domains of the receptor-like transmembrane phosphotyrosine phosphatases. Second, cell-permeable tumor promoters, such as okadaic acid, were shown to be potent phosphatase inhibitors that have multiple effects on signaling pathways. Third, the subunits of the type 2A phosphatase were found to associate with transforming antigens encoded by DNA tumor viruses, indicating a role for phosphatases in mediating abnormal proliferative events. Fourth, several cell-cycle mutants were found to encode phosphatases. This review focuses on the significance of the transmembrane phosphotyrosine phosphatases and on the possible ways in which intracellular phosphatases function in signaling pathways.