Identifying a new tumor suppressor gene is simply the end of the beginning as far as understanding its function goes. Take the PTEN gene, for example, which is mutated in glioblastoma, breast and prostate cancer, and in Cowden disease. Shortly after its discovery last year, Tonks and colleagues (Cold Spring Harbor Laboratory, New York) reported that PTEN is a dual-specificity phosphatase—that is, it removes phosphate groups from serine, threonine and tyrosine residues of target proteins. This all made sense because tyrosine phosphatases are thought to act as tumor suppressors by removing phosphates from (and thus deactivating) growth-promoting kinases.

Then, earlier this year, another group showed that PTEN removes a specific phosphate from a lipid, phosphatidylinositol-3,4,5-trisphosphate (PIP3), which (when all three phosphates are in place) activates downstream kinases. Now, reporting in PNAS (95, 13513–13518; 1998), Tonks and co-workers describe a missense mutation in PTEN that wipes out the lipid phosphatase activity yet leaves the protein phosphatase function intact. In other words, PTEN acts in a completely unexpected way to switch off cell growth signals by dephosphorylating phospholipids.