Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA.
J Cell Sci. 2012 Jan 15;125(Pt 2):310-6. doi: 10.1242/jcs.086256. Epub 2012 Jan 20.
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.
蛋白酪氨酸磷酸酶 1B（PTP1B）是一种丰富的非跨膜酶，在调节胰岛素和瘦素信号中起主要作用。最近，我们报道 PTP1B 可被 SUMO 化抑制，并且 SUMO 化的 PTP1B 在内质网（ER）和相邻的核外膜的核周分布中积累，与其在 ER 中的已知定位一致。在这里，我们报告 PTP1B 除了位于 ER 外，还位于核内膜，在核内膜中 PTP1B 被大量 SUMO 化。我们还发现 PTP1B 与核膜内层蛋白 emerin 相互作用，已知 emerin 被酪氨酸磷酸化，并且 PTP1B 的表达水平与 emerin 的酪氨酸磷酸化水平呈负相关。随着细胞接近有丝分裂，PTP1B 的 SUMO 化大大增加，这与 emerin 的酪氨酸磷酸化达到最大值的阶段相对应。此外，表达一种不可 SUMO 化的 PTP1B 突变体大大降低了 emerin 的酪氨酸磷酸化水平。这些结果表明 PTP1B 以 SUMO 化和细胞周期依赖性方式调节关键核内膜蛋白的酪氨酸磷酸化。
