The PTEN and PI3K-α and -γ are signaling proteins that have important roles in fundamental cellular responses such as proliferation, adhesion, cell size regulation and protection from apoptosis, but their role in the heart is unknown. In September 20 Cell, Michael Crackower and colleagues at the University of Toronto, Canada, show that distinct PI3K-PTEN signaling pathways are involved in regulating myocardial contractility and cardiac cell size (Cell, 110:737-749, September 20, 2002).

Crackower et al. used PTEN-heart muscle specific mutant mice, dominant-negative p110α transgenic mice and double-mutant mice. They observed that two independent PI3K signaling pathways exist in cardiomyocytes that can be genetically uncoupled. While the tyrosine kinase-receptor p110-PTEN pathway is a critical regulator of cardiac cell size, the GPCR-linked PI3K-PTEN signaling pathway modulates heart muscle contractility.

These results show that that cardiac hypertrophy and contractility defects could be genetically uncoupled. "The hope is that if you...

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