The conserved phosphoinositide 3-kinase pathway determines heart size in mice
Tetsuo Shioi,Peter M. Kang,Pamela S. Douglas,James Hampe,Claudine M. Yballe,Joel A. Lawitts,Lewis C. Cantley,Seigo Izumo +7 more
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TLDR
The PI3K pathway is necessary and sufficient to promote organ growth in mammals and was associated with comparable increase or decrease in myocyte size in transgenic mice.Abstract:
Phosphoinositide 3-kinase (PI3K) has been shown to regulate cell and organ size in Drosophila, but the role of PI3K in vertebrates in vivo is not well understood. To examine the role of PI3K in intact mammalian tissue, we have created and characterized transgenic mice expressing constitutively active or dominant-negative mutants of PI3K in the heart. Cardiac- specific expression of constitutively active PI3K resulted in mice with larger hearts, while dominant-negative PI3K resulted in mice with smaller hearts. The increase or decrease in heart size was associated with comparable increase or decrease in myocyte size. Cardiomyopathic changes, such as myocyte necrosis, apoptosis, interstitial fibrosis or contractile dysfunction, were not observed in either of the transgenic mice. Thus, the PI3K pathway is necessary and sufficient to promote organ growth in mammals.read more
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The phosphatidylinositol 3-Kinase AKT pathway in human cancer.
Igor Vivanco,Charles L. Sawyers +1 more
TL;DR: Small-molecule therapeutics that block PI3K signalling might deal a severe blow to cancer cells by blocking many aspects of the tumour-cell phenotype.
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The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism
TL;DR: In light of the recent advances in understanding of the function of PI3Ks in the pathogenesis of diabetes and cancer, the exciting therapeutic opportunities for targeting this pathway to treat these diseases are discussed.
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TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
TL;DR: It is shown that TSC1–TSC2 inhibits the p70 ribosomal protein S6 kinase 1 and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation) and these functions are mediated by inhibition of the mammalian target of rapamycin (mTOR).
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Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo.
Sue C. Bodine,Trevor Stitt,Michael Gonzalez,William O. Kline,Gretchen L. Stover,Roy Bauerlein,Elizabeth Zlotchenko,Angus Scrimgeour,John C. Lawrence,David J. Glass,George D. Yancopoulos +10 more
TL;DR: It is concluded that the activation of the Akt/mTOR pathway and its downstream targets, p70S6K and PHAS-1/4E-BP1, is requisitely involved in regulating skeletal muscle fibre size, and that activation of this pathway can oppose muscle atrophy induced by disuse.
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Regulation of cardiac hypertrophy by intracellular signalling pathways
TL;DR: Recent findings in genetically modified animal models implicate important intermediate signal-transduction pathways in the coordination of heart growth following physiological and pathological stimulation.
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TL;DR: It is shown that growth factor activation of the PI3'K/Akt signaling pathway culminates in the phosphorylation of the BCL-2 family member BAD, thereby suppressing apoptosis and promoting cell survival.
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