Regulation of protein tyrosine phosphatase 1B by sumoylation

Shrikrishna Dadke, Sophie Cotteret, Shu Chin Yip, Zahara M. Jaffer, Fawaz Haj, Alexey Ivanov, Frank Rauscher, Ke Shuai, Tony Ng, Benjamin G. Neel, Jonathan Chernoff

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)80-85
Number of pages6
JournalNature Cell Biology
Volume9
Issue number1
DOIs
StatePublished - Jan 2007

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Non-Receptor Type 1 Protein Tyrosine Phosphatase
Sumoylation
Insulin Receptor
Enzymes
Cell Proliferation
Nuclear Pore
Two-Hybrid System Techniques
Proteins
Ubiquitin-Protein Ligases
Receptor Protein-Tyrosine Kinases
Mutant Proteins
Ubiquitin
Oncogenes
Intercellular Signaling Peptides and Proteins
Down-Regulation
Fibroblasts
Insulin

ASJC Scopus subject areas

  • Cell Biology

Cite this

Dadke, S., Cotteret, S., Yip, S. C., Jaffer, Z. M., Haj, F., Ivanov, A., ... Chernoff, J. (2007). Regulation of protein tyrosine phosphatase 1B by sumoylation. Nature Cell Biology, 9(1), 80-85. https://doi.org/10.1038/ncb1522

Regulation of protein tyrosine phosphatase 1B by sumoylation. / Dadke, Shrikrishna; Cotteret, Sophie; Yip, Shu Chin; Jaffer, Zahara M.; Haj, Fawaz; Ivanov, Alexey; Rauscher, Frank; Shuai, Ke; Ng, Tony; Neel, Benjamin G.; Chernoff, Jonathan.

In: Nature Cell Biology, Vol. 9, No. 1, 01.2007, p. 80-85.

Research output: Contribution to journalArticle

Dadke, S, Cotteret, S, Yip, SC, Jaffer, ZM, Haj, F, Ivanov, A, Rauscher, F, Shuai, K, Ng, T, Neel, BG & Chernoff, J 2007, 'Regulation of protein tyrosine phosphatase 1B by sumoylation', Nature Cell Biology, vol. 9, no. 1, pp. 80-85. https://doi.org/10.1038/ncb1522
Dadke S, Cotteret S, Yip SC, Jaffer ZM, Haj F, Ivanov A et al. Regulation of protein tyrosine phosphatase 1B by sumoylation. Nature Cell Biology. 2007 Jan;9(1):80-85. https://doi.org/10.1038/ncb1522
Dadke, Shrikrishna ; Cotteret, Sophie ; Yip, Shu Chin ; Jaffer, Zahara M. ; Haj, Fawaz ; Ivanov, Alexey ; Rauscher, Frank ; Shuai, Ke ; Ng, Tony ; Neel, Benjamin G. ; Chernoff, Jonathan. / Regulation of protein tyrosine phosphatase 1B by sumoylation. In: Nature Cell Biology. 2007 ; Vol. 9, No. 1. pp. 80-85.
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