Cardiovascular Research Advance Access first published online on January 15, 2009
This version [Corrected Proof] published online on January 30, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp014
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Cardiac regulation by phosphoinositide 3-kinases and PTEN
1 Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada T6G 2B7
2 IMBA, Institute for Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria
* Corresponding author. Tel: +1 780 407 8569; fax: +1 780 407 6452. E-mail address: gavin.oudit{at}ualberta.ca
The diverse effects mediated by PI3K/PTEN (phosphoinositide 3-kinase/phosphatase and tensin homologue deleted on chromosome 10) signalling in the heart clearly support an important biological and pathophysiological role for this signalling cascade. PI3Ks are a family of evolutionarily conserved lipid kinases that mediate many cellular responses to physiological and pathophysiological stimuli. Class I PI3K can be activated by either receptor tyrosine kinase/cytokine receptor activation (class IA) or G-protein-coupled receptors (class IB), leading to the generation of phosphatidyl inositol (3,4,5)P3 and recruitment and activation of Akt/protein kinase B, 3'-phosphoinositide-dependent kinase-1 (PDK1), or monomeric G-proteins, and phosphorylation of a wide range of downstream targets including glycogen synthase kinase 3β (GSK3β), mTOR (mammalian target of rapamycin), p70S6 kinase, endothelial nitric oxide synthase, and several anti-apoptotic effectors. Class IA (PI3K
, β, and 
) and class IB (PI3K
) PI3Ks mediate distinct phenotypes in the heart under negative control by the 3'-lipid phosphatase PTEN, which dephosphorylates PtdIns(3,4,5)P3 to generate PtdIns(4,5)P2. PI3K, PI3K, and PTEN are expressed in cardiomyocytes, fibroblasts, endothelial cells, and vascular smooth muscle cells, where they modulate cell survival, hypertrophy, contractility, metabolism, and mechanotransduction. The PI3K/PTEN signalling pathways are involved in a wide variety of diseases including myocardial hypertrophy and contractility, heart failure, and preconditioning. In this review, we discuss the signalling pathways mediated by PI3K class I isoforms and PTEN and their roles in cardiac structure and function.
KEYWORDS P13 kinase; Akt; Signalling; Hypertrophy; Heart failure
Time for primary review: 37 days
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