• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Regulation of protein tyrosine phosphatase 1B by sumoylation.

Protein-tyrosine phosphatase 1B (PTP1B) is an ubiquitously expressed enzyme that negatively regulates growth-factor signalling and cell proliferation by binding to and dephosphorylating key receptor tyrosine kinases, such as the insulin receptor. It is unclear how the activity of PTP1B is regulated. Using a yeast two-hybrid assay, a protein inhibitor of activated STAT1 (PIAS1) was isolated as a PTP1B-interacting protein. Here, we show that PIAS1, which functions as a small ubiquitin-like modifier (SUMO) E3 ligase, associates with PTP1B in mammalian fibroblasts and catalyses sumoylation of PTP1B. Sumoylation of PTP1B reduces its catalytic activity and inhibits the negative effect of PTP1B on insulin receptor signalling and on transformation by the oncogene v-crk. Insulin-stimulated sumoylation of endogenous PTP1B results in a transient downregulation of the enzyme; this event does not occur when the endogenous enzyme is replaced with a sumoylation-resistant mutant of PTP1B. These results suggest that sumoylation, which has been implicated primarily in processes in the nucleus and nuclear pore, also modulates a key enzyme-substrate signalling complex that regulates metabolism and cell proliferation.

Pubmed ID: 17159996


  • Dadke S
  • Cotteret S
  • Yip SC
  • Jaffer ZM
  • Haj F
  • Ivanov A
  • Rauscher F
  • Shuai K
  • Ng T
  • Neel BG
  • Chernoff J


Nature cell biology

Publication Data

January 2, 2007

Associated Grants

  • Agency: Medical Research Council, Id: G0100152

Mesh Terms

  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Gene Expression Regulation, Enzymologic
  • Mice
  • Microscopy, Fluorescence, Multiphoton
  • Protein Inhibitors of Activated STAT
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • SUMO-1 Protein
  • Signal Transduction
  • Transfection