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• W2000514975 abstract "H11 kinase/Hsp22 (H11K) is a chaperone promoting cardiac cell growth and survival through the activation of Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K). In this study, we tested whether H11K-induced activation of the PI3K/Akt pathway is mediated by the bone morphogenetic protein (BMP) signaling, both in a transgenic mouse model with cardiac-specific overexpression of H11K and in isolated cardiac myocytes. Microarrays in hearts from transgenic compared to wild-type mice showed an upregulation of the BMP receptors Alk3 and BMPR-II, and of their ligand BMP4 ( P <0.01 versus wild type). Activation of the BMP pathway in transgenic mice was confirmed by increased phosphorylation of the “canonical” BMP effectors Smad 1/5/8 ( P <0.01 versus wild type). In isolated myocytes, adenovirus-mediated overexpression of H11K was accompanied by a significant ( P <0.01) increase in PI3K activity, phospho-Akt, Smad 1/5/8 phosphorylation and [ 3 H]phenylalanine incorporation, and by a 70% reduction in H 2 O 2 -mediated apoptosis. All these effects were abolished by the BMP antagonist noggin. In presence of BMP4, Smad 1/5/8 phosphorylation was enhanced by 5-fold on H11K overexpression but decreased by 3-fold on H11K knockdown ( P <0.01 versus control), showing that H11K potentiates the BMP signaling. In pull-down experiments, H11K increased both the association of Alk3 and BMPR-II together, and their interaction with the transforming growth factor-β–activated kinase (TAK)1, a “noncanonical” mediator of the BMP receptor signaling. TAK1 inhibition prevented H11K-mediated activation of Akt. Therefore, potentiation of the BMP receptor by H11K promotes an activation of the PI3K/Akt pathway mediated by TAK1, which dictates the physiological effects of H11K on cardiac cell growth and survival." @default.
• W2000514975 created "2016-06-24" @default.
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• W2000514975 date "2009-04-10" @default.
• W2000514975 modified "2023-10-16" @default.
• W2000514975 title "Activation of the Bone Morphogenetic Protein Receptor by H11Kinase/Hsp22 Promotes Cardiac Cell Growth and Survival" @default.
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• W2000514975 doi "https://doi.org/10.1161/circresaha.108.192328" @default.
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