Calcineurin dephosphorylates multiple serine residues near the N terminus of NFAT proteins enabling them to translocate from cytoplasm to nucleus, where they activate a subset of hypertrophic response genes. Transgeni...Calcineurin dephosphorylates multiple serine residues near the N terminus of NFAT proteins enabling them to translocate from cytoplasm to nucleus, where they activate a subset of hypertrophic response genes. Transgenic mice over-expressing a constitu- tively active form of calcineurin or NFAT3, developed obviously hypertrophy and heart failure or sudden death proving its pathogenic role. Here we used literatures on MEDLINE （2000-2011）, systematically reviewed the new development of calcineurin signaling pathway in myocardial hypertrophy展开更多
RCAN1, also known as DSCR1, is an endogenous regulator of calcineurin, a serine/threonine protein phosphatase that plays a critical role in many physiological processes. In this report, we demonstrate that p38a MAP ki...RCAN1, also known as DSCR1, is an endogenous regulator of calcineurin, a serine/threonine protein phosphatase that plays a critical role in many physiological processes. In this report, we demonstrate that p38a MAP kinase can phosphorylate RCAN1 at multiple sites in vitro and show that phospho-RCAN1 is a good protein substrate for calcineurin. In addition, we found that unphosphorylated RCANI noncompetitively inhibits calcineurin protein phosphatase activity and that the phosphorylation of RCAN1 by p38a MAP kinase decreases the binding affinity of RCAN1 for calcineurin. These findings reveal the molecular mechanism by which p38a MAP kinase regulates the function of RCAN1/calcineurin through phosphorylation.展开更多
文摘Calcineurin dephosphorylates multiple serine residues near the N terminus of NFAT proteins enabling them to translocate from cytoplasm to nucleus, where they activate a subset of hypertrophic response genes. Transgenic mice over-expressing a constitu- tively active form of calcineurin or NFAT3, developed obviously hypertrophy and heart failure or sudden death proving its pathogenic role. Here we used literatures on MEDLINE （2000-2011）, systematically reviewed the new development of calcineurin signaling pathway in myocardial hypertrophy
基金supported in part by Ministry of Science and Technology of China (Grant 2011CB910803)
文摘RCAN1, also known as DSCR1, is an endogenous regulator of calcineurin, a serine/threonine protein phosphatase that plays a critical role in many physiological processes. In this report, we demonstrate that p38a MAP kinase can phosphorylate RCAN1 at multiple sites in vitro and show that phospho-RCAN1 is a good protein substrate for calcineurin. In addition, we found that unphosphorylated RCANI noncompetitively inhibits calcineurin protein phosphatase activity and that the phosphorylation of RCAN1 by p38a MAP kinase decreases the binding affinity of RCAN1 for calcineurin. These findings reveal the molecular mechanism by which p38a MAP kinase regulates the function of RCAN1/calcineurin through phosphorylation.
