A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 31/5377 (2006.01) A61K 31/00 (2006.01) A61K 31/343 (2006.01) A61K 31/352 (2006.01) A61K 31/353 (2006.01) A61K 31/5375 (2006.01) A61K 31/585 (2006.01) A61K 31/7088 (2006.01) A61K 38/17 (2006.01) A61K 38/45 (2006.01) A61K 39/395 (2006.01) A61P 9/00 (2006.01) A61P 9/06 (2006.01) A61P 9/12 (2006.01) C07K 14/47 (2006.01) C12N 9/12 (2006.01) C12N 9/16 (2006.01) C12N 15/85 (2006.01) C12Q 1/50 (2006.01) C12Q 1/68 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2400254
The PTEN/PI3K signaling pathway regulates a vast array of fundamental cellular responses. We show that cardiomyocyte-specific inactivation of tumor suppressor PTEN results in hypertrophy, and unexpectedly, a dramatic decrease in cardiac contractility. Analysis of double mutant mice revealed that the cardiac hypertrophy and the contractility defects can be genetically uncoupled. PI3K.gamma. mediates the alteration in cell size while PI3K.gamma.acts as a negative regulator of cardiac contractility. Mechanistically, PI3K.gamma. inhibits cAMP production and hypercontractility can be reverted by blocking cAMP function. These data show that PTEN has an important in vivo role in cardiomyocyte hypertrophy and GPCR signaling and identify a function for the PTEN-PI3K.gamma. pathway in the modulation of heart muscle contractility.
Crackower Michael
Penninger Josef
Amgen Canada Inc.
Bereskin & Parr
Crackower Michael
Penninger Josef
University Health Network
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