Membrane localization of protein-tyrosine phosphatase 1B is essential for its activation of sterol regulatory element-binding protein-1 gene expression
Membrane localization of protein-tyrosine phosphatase 1B is essential for its activation of sterol regulatory element-binding protein-1 gene expression
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DOI：
10.1016/j.bbrc.2007.09.015
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发表时间：
2007-11-23
影响因子：
3.1
通讯作者：
Maegawa, H.
中科院分区：
文献类型：
--
作者：
Shi, K.;Ugi, S.;Maegawa, H.
固醇调节元件结合蛋白-1（SREBP-1）是刺激肝脏脂肪生成的关键转录因子。蛋白酪氨酸磷酸酶1B（PTP 1B）通过蛋白磷酸酶2A（PP 2A）激活诱导SREBP-I基因表达。据报道，PTP 1B通过其C-末端尾锚定在内质网（ER）上，并且通过C-末端截短改变PTP 1B的细胞内定位不会改变其对胰岛素信号传导的抑制作用。在这项研究中，我们研究了PTP 1B细胞内定位的变化是否会影响SREBP-1基因的表达。在大鼠Fao细胞中过表达C-末端截短的PTP 1B（PTP 1BACT）不会诱导SREBP-1基因表达。此外，PTP 1B Delta CT未能结合PP 2A，导致PP 2A活化受损，而野生型PTP 1B（PTP 1BWT）的过表达与PP 2A相关。此外，膜靶向的PTP 1B Delta CT激活了PP 2A，并恢复了PP 2A结合，尽管缺乏其C末端区域。最后，PTP 1B Delta CT在小鼠原代培养肝细胞中的过表达未能增强SREBP-1c mRNA，而膜靶向PTP 1B Delta CT导致肝细胞和PTP 1BWT中SREBP-1c mRNA的增强。总之，PTP 1B的膜定位是PP 2A激活所必需的，这是其增强SREBP-I基因表达的关键。(C)2007年爱思唯尔公司All rights reserved.
Sterol regulatory element-binding protein-1 (SREBP-1) is a key transcription factor in stimulating lipogenesis in the liver. Protein-tyrosine phosphatase 1B (PTP1B) induces SREBP-I gene expression via protein phosphatase 2A (PP2A) activation. PTP1B is reported to be anchored on the endoplasmic reticulum (ER) via its C-terminal tail, and change in intracellular localization of PTP1B by C-terminal-truncation did not alter its inhibitory effects on insulin signaling. In this study, we investigated whether the change in intracellular localization of PTP1B could influence SREBP-1 gene expression. Overexpression of C-terminal truncated PTP1B (PTP1BACT) in rat Fao cells did not induce SREBP-1 gene expression. Furthermore, PTP1B Delta CT failed to bind PP2A, resulting in impaired PP2A activation, whereas overexpression of wild-type PTP1B (PTP1BWT) associated with PP2A. Moreover, a membrane-targeted PTP1B Delta CT activated PP2A with restored PP2A binding, despite the absence of its C-terminal region. Finally, overexpression of PTP1B Delta CT into mouse primary cultured hepatocytes failed to enhance SREBP-1c mRNA, whereas membrane-targeted PTP1B Delta CT led to enhanced SREBP-1c mRNA in hepatocytes as well as PTP1BWT. In conclusion, membrane localization of PTP1B is essential for PP2A activation, which is crucial for its enhancement of SREBP-I gene expression. (C) 2007 Elsevier Inc. All rights reserved.