Deletion of Shp2 Tyrosine Phosphatase in Muscle Leads to Dilated Cardiomyopathy, Insulin Resistance, and Premature Death

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	Deletion of Shp2 Tyrosine Phosphatase in Muscle Leads to Dilated Cardiomyopathy, Insulin Resistance, and Premature Death
	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 ; Chen, Yan ; Reed, John C. ; Tong, Gary G. ; Mercola, Mark ; Chen, Ju ; Feng, Gen-Sheng ; Wang J(王军)
刊名	http://dx.doi.org/10.1128/MCB.01661-08
	2009-01-15
关键词	ACTIVATED PROTEIN-KINASE HEART-FAILURE CARDIAC-HYPERTROPHY SIGNALING PATHWAYS RECEPTOR SUBSTRATE-1 GENE-EXPRESSION PTPN11 SHP2 CARDIOMYOCYTES MOUSE MECHANISM
英文摘要	NIH [R01DK73945, R01HL082902, R01HL059502]; American Heart Association; AHA National Scientist Development; 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.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/60520]
专题	海洋环境－已发表论文
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]. http://dx.doi.org/10.1128/MCB.01661-08,2009.
APA	Princen, Frederic.,Bard, Emilie.,Sheikh, Farah.,Zhang, Sharon S..,Wang, Jing.,...&王军.(2009).Deletion of Shp2 Tyrosine Phosphatase in Muscle Leads to Dilated Cardiomyopathy, Insulin Resistance, and Premature Death.http://dx.doi.org/10.1128/MCB.01661-08.
MLA	Princen, Frederic,et al."Deletion of Shp2 Tyrosine Phosphatase in Muscle Leads to Dilated Cardiomyopathy, Insulin Resistance, and Premature Death".http://dx.doi.org/10.1128/MCB.01661-08 (2009).