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Deletion of Shp2 Tyrosine Phosphatase in Muscle Leads to Dilated Cardiomyopathy, Insulin Resistance, and Premature Death
文献类型：期刊论文
| 作者 | Princen, Frederic; Bard, Emilie; Sheikh, Farah; Zhang, Sharon S.; Wang, Jing; Zago, Wagner M.; Wu, Dongmei; Trelles, Ramon Diaz; Bailly-Maitre, Beatrice; Kahn, C. Ronald |
| 刊名 | MOLECULAR AND CELLULAR BIOLOGY
 |
| 出版日期 | 2009 |
| 卷号 | 29期号:2页码:378-388 |
| 英文摘要 | The intracellular signaling mechanisms underlying the pathogenesis of cardiac diseases are not fully understood. We report here that selective deletion of Shp2, an SH2-containing cytoplasmic tyrosine phosphatase, in striated muscle results in severe dilated cardiomyopathy in mice, leading to heart failure and premature mortality. Development of cardiomyopathy in this mouse model is coupled with insulin resistance, glucose intolerance, and impaired glucose uptake in striated muscle cells. Shp2 deficiency leads to upregulation of leukemia inhibitory factor-stimulated phosphatidylinositol 3-kinase/Akt, Erk5, and Stat3 pathways in cardiomyocytes. Insulin resistance and impaired glucose uptake in Shp2-deficient mice are at least in part due to impaired protein kinase C-zeta/lambda and AMP-kinase activities in striated muscle. Thus, we have generated a mouse line modeling human patients suffering from cardiomyopathy and insulin resistance. This study reinforces a concept that a compound disease with multiple cardiovascular and metabolic disturbances can be caused by a defect in a single molecule such as Shp2, which modulates multiple signaling pathways initiated by cytokines and hormones. |
| 类目[WOS] | Biochemistry & Molecular Biology ; Cell Biology |
| 关键词[WOS] | ACTIVATED PROTEIN-KINASE ; HEART-FAILURE ; CARDIAC-HYPERTROPHY ; SIGNALING PATHWAYS ; RECEPTOR SUBSTRATE-1 ; GENE-EXPRESSION ; PTPN11 SHP2 ; CARDIOMYOCYTES ; MOUSE ; MECHANISM |
| 语种 | 英语 |
| WOS记录号 | WOS:000262045800007 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/89]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_信号转导与营养相关疾病研究组 |
| 推荐引用方式 GB/T 7714 | Princen, Frederic,Bard, Emilie,Sheikh, Farah,et al. Deletion of Shp2 Tyrosine Phosphatase in Muscle Leads to Dilated Cardiomyopathy, Insulin Resistance, and Premature Death[J]. MOLECULAR AND CELLULAR BIOLOGY,2009,29(2):378-388. |
| APA | Princen, Frederic.,Bard, Emilie.,Sheikh, Farah.,Zhang, Sharon S..,Wang, Jing.,...&Feng, Gen-Sheng.(2009).Deletion of Shp2 Tyrosine Phosphatase in Muscle Leads to Dilated Cardiomyopathy, Insulin Resistance, and Premature Death.MOLECULAR AND CELLULAR BIOLOGY,29(2),378-388. |
| MLA | Princen, Frederic,et al."Deletion of Shp2 Tyrosine Phosphatase in Muscle Leads to Dilated Cardiomyopathy, Insulin Resistance, and Premature Death".MOLECULAR AND CELLULAR BIOLOGY 29.2(2009):378-388. |
入库方式： OAI收割
来源：上海营养与健康研究所
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