کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2191046 1097840 2010 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The mAKAPβ scaffold regulates cardiac myocyte hypertrophy via recruitment of activated calcineurin
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
The mAKAPβ scaffold regulates cardiac myocyte hypertrophy via recruitment of activated calcineurin
چکیده انگلیسی

mAKAPβ is the scaffold for a multimolecular signaling complex in cardiac myocytes that is required for the induction of neonatal myocyte hypertrophy. We now show that the pro-hypertrophic phosphatase calcineurin binds directly to a single site on mAKAPβ that does not conform to any of the previously reported consensus binding sites. Calcineurin–mAKAPβ complex formation is increased in the presence of Ca2+/calmodulin and in norepinephrine-stimulated primary cardiac myocytes. This binding is of functional significance because myocytes exhibit diminished norepinephrine-stimulated hypertrophy when expressing a mAKAPβ mutant incapable of binding calcineurin. In addition to calcineurin, the transcription factor NFATc3 also associates with the mAKAPβ scaffold in myocytes. Calcineurin bound to mAKAPβ can dephosphorylate NFATc3 in myocytes, and expression of mAKAPβ is required for NFAT transcriptional activity. Taken together, our results reveal the importance of regulated calcineurin binding to mAKAPβ for the induction of cardiac myocyte hypertrophy. Furthermore, these data illustrate how scaffold proteins organizing localized signaling complexes provide the molecular architecture for signal transduction networks regulating key cellular processes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 48, Issue 2, February 2010, Pages 387–394
نویسندگان
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