title: Sumoylated protein tyrosine phosphatase 1B localizes to the inner nuclear membrane and regulates the tyrosine phosphorylation of emerin.
abstract: Protein tyrosine phosphatase (PTP)1B is an abundant non-transmembrane enzyme that plays a major role in regulating insulin and leptin signaling. Recently, we reported that PTP1B is inhibited by sumoylation, and that sumoylated PTP1B accumulates in a perinuclear distribution, consistent with its known localization in the endoplasmic reticulum (ER) and the contiguous outer nuclear membrane. Here, we report that, in addition to its localization at the ER, PTP1B also is found at the inner nuclear membrane, where it is heavily sumoylated. We also find that PTP1B interacts with emerin, an inner nuclear membrane protein that is known to be tyrosine phosphorylated, and that PTP1B expression levels are inversely correlated with tyrosine phosphorylation levels of emerin. PTP1B sumoylation greatly increases as cells approach mitosis, corresponding to the stage where tyrosine phosphorylation of emerin is maximal. In addition, expression of a non-sumoylatable mutant of PTP1B greatly reduced levels of emerin tyrosine phosphorylation. These results suggest that PTP1B regulates the tyrosine phosphorylation of a key inner nuclear membrane protein in a sumoylation- and cell-cycle-dependent manner.
authors.affiliation: Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA.
authors.forename: Shu-Chin
authors.initials: SC
authors.lastname: Yip
authors.forename: Sophie
authors.initials: S
authors.lastname: Cotteret
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chernoff
mesh_terms: D000818:Animals; D002453:Cell Cycle; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009685:Nuclear Envelope / Q000201:enzymology*; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D009687:Nuclear Proteins; C092710:emerin; D014443:Tyrosine; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse