Letter abstract

Nature Cell Biology 9, 80 - 85 (2006)
Published online: 10 December 2006 | doi:10.1038/ncb1522

Regulation of protein tyrosine phosphatase 1B by sumoylation

Shrikrishna Dadke1,6,8, Sophie Cotteret1,8, Shu-Chin Yip1, Zahara M. Jaffer1, Fawaz Haj2,7, Alexey Ivanov3, Frank Rauscher, III3, Ke Shuai4, Tony Ng5, Benjamin G. Neel2 & Jonathan Chernoff1

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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 receptor1. It is unclear how the activity of PTP1B is regulated. Using a yeast two-hybrid assay, a protein inhibitor of activated STAT1 (PIAS1)2 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.

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  1. Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
  2. Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, New Research Building, Rm # 1030, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
  3. Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104, USA.
  4. Division of Hematology-Oncology, University of California Los Angeles, 11-934 Factor Building, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
  5. Randall Division of Cell and Molecular Biophysics, Guy's Campus, King's College, London, SE1 1UL, UK.
  6. Current address: Diabetes Research Program, Stem Cell Research Center, 9th Floor, Manipal Hospital, Airport Road, Bangalore 560017, Karnataka, India.
  7. Current address: University of California at Davis, Nutrition Department, 3135 Meyer Hall, One Shields Avenue, Davis, CA 95616, USA.
  8. These authors contributed equally to this work.

Correspondence to: Jonathan Chernoff1 e-mail: J_Chernoff@fccc.edu



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