Deletion of Shp2 tyrosine phosphatase in muscle leads to dilated cardiomyopathy, insulin resistance, and premature death.


: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.


Mol Cell Biol


Princen F,Bard E,Sheikh F,Zhang SS,Wang J,Zago WM,Wu D,Trelles RD,Bailly-Maitre B,Kahn CR,Chen Y,Reed JC,Tong GG,Mercola M,Chen J,Feng GS




Has Abstract


2009-01-01 00:00:00














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    abstract::p21Sdi1/WAF1/Cip1 inhibits cyclin-dependent protein kinases and cell proliferation. p21 is presumed to inhibit growth by preventing the phosphorylation of growth-regulatory proteins, including the retinoblastoma tumor suppressor protein (pRb). The ultimate effector(s) of p21 growth inhibition, however, is largely a ma...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    更新日期:1994-11-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    更新日期:2002-09-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    更新日期:2013-11-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Yao KM,White K

    更新日期:1991-06-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    更新日期:1994-04-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Zhan Y,Cleveland JL,Stevens JL

    更新日期:1997-11-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Guo Y,Breeden LL,Zarbl H,Preston BD,Eaton DL

    更新日期:2005-07-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Mu W,Wang W,Schimenti JC

    更新日期:2008-10-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Brown CE,Sachs AB

    更新日期:1998-11-01 00:00:00

  • The gene encoding the transcription factor SCIP has features of an expressed retroposon.

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


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    更新日期:1991-09-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Zweidler-Mckay PA,Grimes HL,Flubacher MM,Tsichlis PN

    更新日期:1996-08-01 00:00:00

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    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Larsen JV,Hansen M,Møller B,Madsen P,Scheller J,Nielsen M,Petersen CM

    更新日期:2010-09-01 00:00:00