PTP-S2, a nuclear tyrosine phosphatase, is phosphorylated and excluded from condensed chromosomes during mitosis

PTP-S2 is a tyrosine specific protein phosphatase that binds to DNA and is localized to the nucleus in association with chromatin. It plays a role in the regulation of cell proliferation. Here we show that the subcellular dis tribution of this protein changes during cell division. While PTP-S2 was lo calized exclusively to the nucleus in interphase cells, during metaphase an d anaphase it was distributed throughout the cytoplasm and excluded from co ndensed chromosomes. At telophase PTP-S2 began to associate with chromosome s and at cytokinesis it was associated with chromatin in the newly formed n ucleus. It was hyperphosphorylated and showed retarded mobility in cells ar rested in metaphase. In vitro experiments showed that it was phosphorylated by CK2 resulting in mobility shift. Using a deletion mutant we found that CK2 phosphorylated PTP-S2 in the C-terminal noncatalytic domain. A heparin sensitive kinase from mitotic cell extracts phosphorylated PTP-S2 resulting in mobility shift. These results are consistent with the suggestion that d uring metaphase PTP-S2 is phosphorylated (possibly by CK2 or a CK2-like enz yme), resulting in its dissociation from chromatin.