Pin1 acts catalytically to promote a conformational change in Cdc25

Pin1 is an essential protein that can peptidyl-prolyl-isomerize small phosp hopeptides. It has been suggested that Pin1 regulates entry into mitosis by catalyzing the cis/trans-isomerization of prolines on critical protein sub strates in response to phosphorylation. We show that Pin1 catalytically gen erates a conformational change on the mitotic phosphatase Cdc25, as assayed by limited protease digestion, differential reactivity to a phosphoserine- proline-directed monoclonal antibody (MPM-2), and by changes in Cdc25 enzym atic activity. Pin1 catalytically modifies the conformation of Cdc25 at sto ichiometries less than 0.0005, and mutants of Pin1 in the prolyl isomerase domain are not active. We suggest that, although difficult to detect, phosp horylation-dependent conformational changes mediated by prolyl isomerizatio n may play an important regulatory role in the cell cycle.