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 distribution of this protein changes during cell division. While PTP-S2 was localized exclusively to the nucleus in interphase cells, during metaphase and anaphase it was distributed throughout the cytoplasm and excluded from condensed chromosomes. At telophase PTP-S2 began to associate with chromosomes and at cytokinesis it was associated with chromatin in the newly formed nucleus. It was hyperphosphorylated and showed retarded mobility in cells arrested 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 non-catalytic domain. A heparin sensitive kinase from mitotic cell extracts phosphorylated PTP-S2 resulting in mobility shift. These results are consistent with the suggestion that during metaphase PTP-S2 is phosphorylated (possibly by CK2 or a CK2-like enzyme), resulting in its dissociation from chromatin.
Nambirajan
S
S
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
Radha
V
V
Kamatkar
S
S
Swarup
G
G
D000595:Amino Acid Sequence; D000818:Animals; D047390:Casein Kinase II; D020134:Catalytic Domain; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D002843:Chromatin / Q000201:enzymology; D002875:Chromosomes / Q000201:enzymology*; D005347:Fibroblasts / Q000201:enzymology; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D018613:Microscopy, Confocal; D008938:Mitosis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats
D002843:Chromatin; D007527:Isoenzymes; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases