Prohibitin is involved in the activated internalization and degradation of protease-activated receptor 1
文献类型：期刊论文
| 作者 | Wang YJ1; Guo XL1,2; Li SA1; Zhao YQ3; Liu ZC4; Lee WH1; Xiang Y[*]1; Zhang Y[*]1 |
| 刊名 | BIOCHIMICA ET BIOPHYSICA ACTA
 |
| 出版日期 | 2014 |
| 卷号 | 1843期号:7页码:1393-1401 |
| 关键词 | Activated internalization Erk1/2 signaling degradation PAR1 Prohibitin |
| 通讯作者 | yang_xiang000@hotmail.com ; zhangy@mail.kiz.ac.cn |
| 英文摘要 | The protease-activated receptor 1 (PAR1) is a G-protein-coupled receptor that is irreversibly activated by either thrombin or metalloprotease 1. Due this irrevocable activation, activated internalization and degradation are critical for PAR1 signaling termination. Prohibitin (PHB) is an evolutionarily conserved, ubiquitously expressed, pleiotropic protein and belongs to the stomatin/prohibitin/flotillin/HflK/C (SPFH) domain family. In a previous study, we found that PHB localized on the platelet membrane and participated in PAR1-mediated human platelet aggregation, suggesting that PHB likely regulates the signaling of PAR1. Unfortunately, PHB's exact function in PAR1 internalization and degradation is unclear. In the current study, flow cytometry revealed that PHB expressed on the surface of endothelial cells (HUVECs) but not cancer cells (MDA-MB-231). Further confocal microscopy revealed that PHB dynamically associates with PAR1 in a time-dependent manner following induction with PAR1-activated peptide (PAR1-AP), though differently between HUVECs and MDA-MB-231 cells. Depletion of PHB by RNA interference significantly inhibited PAR1 activated internalization and led to sustained Erk1/2 phosphorylation in the HUVECs; however, a similar effect was not observed in MDA-MB-231 cells. For both the endothelial and cancel cells, PHB repressed PAR1 degradation, while knockdown of PHB led to increased PAR1 degradation, and PHB overexpression inhibited PAR1 degradation. These results suggest that persistent PAR1 signaling due to the absence of membrane PHB and decreased PAR1 degradation caused by the upregulation of intracellular PHB in cancer cells (such as MDA-MB-231 cells) may render cells highly invasive. As such, PHB may be a novel target in future anti-cancer therapeutics, or in more refined cancer malignancy diagnostics. |
| 资助信息 | This work was supported by grants from the National Natural Science FoundationofChina(31270835,NSFC-YunnanjointfundingU1132601), the Key Research Program of the Chinese Academy of Sciences (KJZD- EW-L03), and the National Basic Research Program of China (973 Pro- gram, 2010CB529800). |
| 语种 | 英语 |
| WOS记录号 | WOS:000336713600016 |
| 公开日期 | 2014-06-04 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7868]  |
| 专题 | 昆明动物研究所_动物活性蛋白多肽组学 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 昆明动物研究所_遗传资源与进化国家重点实验室 昆明动物研究所_结构生物信息学 |
| 作者单位 | 1.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650223, China 2.Kunming College of Life Science, University of Chinese Academy of Sciences Kunming, Yunnan 650204, China 3.State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650223, China 4.Department of Life Science and Technology, Kunming University, Kunming, Yunnan 650214, China |
| 推荐引用方式 GB/T 7714 | Wang YJ,Guo XL,Li SA,et al. Prohibitin is involved in the activated internalization and degradation of protease-activated receptor 1[J]. BIOCHIMICA ET BIOPHYSICA ACTA,2014,1843(7):1393-1401. |
| APA | Wang YJ.,Guo XL.,Li SA.,Zhao YQ.,Liu ZC.,...&Zhang Y[*].(2014).Prohibitin is involved in the activated internalization and degradation of protease-activated receptor 1.BIOCHIMICA ET BIOPHYSICA ACTA,1843(7),1393-1401. |
| MLA | Wang YJ,et al."Prohibitin is involved in the activated internalization and degradation of protease-activated receptor 1".BIOCHIMICA ET BIOPHYSICA ACTA 1843.7(2014):1393-1401. |
入库方式： OAI收割
来源：昆明动物研究所
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