Translocation of protein tyrosine phosphatase Pez/PTPD2/PTP36 to the nucleus is associated with induction of cell proliferation.
Pez is a non-transmembrane tyrosine phosphatase with homology to the FERM (4.1, ezrin, radixin, moesin) family of proteins. The subcellular localisation of Pez in endothelial cells was found to be regulated by cell density and serum concentration. In confluent monolayers Pez was cytoplasmic, but in cells cultured at low density Pez was nuclear, suggesting that it is a nuclear protein in proliferating cells. This notion is supported by the loss of nuclear Pez when cells are serum-starved to induce quiescence, and the rapid return of Pez to the nucleus upon refeeding with serum to induce proliferation. Vascular endothelial cells normally exist as a quiescent confluent monolayer but become proliferative during angiogenesis or upon vascular injury. Using a 'wound' assay to mimic these events in vitro, Pez was found to be nuclear in the cells that had migrated and were proliferative at the 'wound' edge. TGFbeta, which inhibits cell proliferation but not migration, inhibited the translocation of Pez to the nucleus in the cells at the 'wound' edge, further strengthening the argument that Pez plays a role in the nucleus during cell proliferation. Together, the data presented indicate that Pez is a nuclear tyrosine phosphatase that may play a role in cell proliferation.
Wadham
C
C
Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Frome Road, Adelaide, SA 5000, Australia.
Gamble
J R
JR
Vadas
M A
MA
Khew-Goodall
Y
Y
D000906:Antibodies / Q000276:immunology; D001692:Biological Transport / Q000187:drug effects; D002452:Cell Count; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000906:Antibodies; D003470:Culture Media; D016895:Culture Media, Serum-Free; D016212:Transforming Growth Factor beta; C093261:PTPN14 protein, human; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor