Regulation of protein tyrosine phosphatase 1B by sumoylation

Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Nature Cell Biology (Impact Factor: 20.06). 02/2007; 9(1):80-5. DOI: 10.1038/ncb1522
Source: PubMed

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.

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Available from: Jonathan Chernoff, Aug 08, 2015
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    • "Although most SUMOylation substrates identified so far are nuclear proteins, the enzymes involved in SUMOylation are indeed present in the cytoplasm (Melchior et al., 2003; Johnson, 2004; Geiss-Friedlander and Melchior, 2007). Several pieces of evidence suggested distinct roles for SUMOylation in several cytoplasmic compartments, including mitochondria (Harder et al., 2004; Zunino et al., 2007) and ER (Dadke et al., 2007). SUMOylation is also implicated in regulating intermediate filament (Kaminsky et al., 2009), membrane receptors, and ion channels (Rajan et al., 2005; Benson et al., 2007; Martin et al., 2007). "
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    The Journal of Cell Biology 11/2012; 200(3). DOI:10.1083/jcb.201203150 · 9.69 Impact Factor
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    • "Expression vectors encoding T7-tagged SUMO1, wild-type pCMV6-HA-PTP1B and the sumoylation-resistant mutant HA-PTP1B-K4R have been described previously (Dadke et al., 2007). pEGFP–emerin was a gift from Yuichi "
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    Journal of Cell Science 01/2012; 125(Pt 2):310-6. DOI:10.1242/jcs.086256 · 5.33 Impact Factor
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    • "This is quite the opposite of the findings in the present study which reveals the importance of careful selection of internal controls specifically for the particular conditions of a given experiment. The decrease in transcription of the Ubc gene is of interest as the ubiquitin proteasome pathway (UPP) plays an essential role in the fine tuning of cellular functions and signalling pathways by regulating the intracellular levels of a wide range of proteins , including those involved in the control of the cell cycle, transcriptional activation, apoptosis, and cell signalling (Smalle and Vierstra 2004; Jin et al. 2006; Dadke et al. 2007). Furthermore, several lines of evidence highlight the importance of the ubiquitin–proteasome pathway in pathogen–plant interactions and host defence mechanisms (Goritschnig et al. 2007; Lee et al. 2007; Delaure et al. 2008). "
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