کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8473864 | 1550413 | 2016 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
RSK3 is required for concentric myocyte hypertrophy in an activated Raf1 model for Noonan syndrome
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: RSK3 is required for concentric myocyte hypertrophy in an activated Raf1 model for Noonan syndrome RSK3 is required for concentric myocyte hypertrophy in an activated Raf1 model for Noonan syndrome](/preview/png/8473864.png)
چکیده انگلیسی
Noonan syndrome (NS) is a congenital disorder resulting from mutations of the Ras-Raf signaling pathway. Hypertrophic cardiomyopathy associated with RAF1 “RASopathy” mutations is a major risk factor for heart failure and death in NS and has been attributed to activation of MEK1/2-ERK1/2 mitogen-activated protein kinases. We recently discovered that type 3 p90 ribosomal S6 kinase (RSK3) is an ERK effector that is required, like ERK1/2, for concentric myocyte hypertrophy in response to pathological stress such as pressure overload. In order to test whether RSK3 also contributes to NS-associated hypertrophic cardiomyopathy, RSK3 knock-out mice were crossed with mice bearing the Raf1L613V human NS mutation. We confirmed that Raf1L613V knock-in confers a NS-like phenotype, including cardiac hypertrophy. Active RSK3 was increased in Raf1L613V mice. Constitutive RSK3 gene deletion prevented the Raf1L613V-dependent concentric growth in width of the cardiac myocyte and attenuated cardiac hypertrophy in female mice. These results are consistent with RSK3 being an important mediator of ERK1/2-dependent growth in RASopathy. In conjunction with previously published data showing that RSK3 is important for pathological remodeling of the heart, these data suggest that targeting of this downstream MAP-kinase pathway effector should be considered in the treatment of RASopathy-associated hypertrophic cardiomyopathy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 93, April 2016, Pages 98-105
Journal: Journal of Molecular and Cellular Cardiology - Volume 93, April 2016, Pages 98-105
نویسندگان
Catherine L. Passariello, Eliana C. Martinez, Hrishikesh Thakur, Maria Cesareo, Jinliang Li, Michael S. Kapiloff,