@article{d9e378cd9b6245bc989253939dd3b283,
title = "Regulation of myocardial contractility and cell size by distinct PI3K-PTEN signaling pathways",
abstract = "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 could be genetically uncoupled. PI3Kα mediates the alteration in cell size while PI3Kγ acts as a negative regulator of cardiac contractility. Mechanistically, PI3Kγ 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-PI3Kγ pathway in the modulation of heart muscle contractility.",
author = "Crackower, \{Michael A.\} and Oudit, \{Gavin Y.\} and Ivona Kozieradzki and Renu Sarao and Hui Sun and Takehiko Sasaki and Emilio Hirsch and Akira Suzuki and Tetsuo Shioi and Junko Irie-Sasaki and Rajan Sah and Cheng, \{Hai Ying M.\} and Rybin, \{Vitalyi O.\} and Giuseppe Lembo and Luigi Fratta and Oliveira-dos-Santos, \{Antonio J.\} and Benovic, \{Jeffery L.\} and Kahn, \{C. Ronald\} and Seigo Izumo and Steinberg, \{Susan F.\} and Wymann, \{Matthias P.\} and Backx, \{Peter H.\} and Penninger, \{Josef M.\}",
note = "Funding Information: We thank T. Wada, K Bachmaier, and S. Backman for helpful discussions. This study was supported by Amgen and by grants from American Heart Association and the NIH HL28958 to S.F.S. S.I. is supported by an NIH Grant, HL 65742. J.M.P. was supported by Amgen Inc., the National Cancer Institute of Canada, and IMBA, Vienna. J.M.P. holds a Canadian Research Chair in Cell Biology. M.A.C. is supported in part by a Canadian Institutes of Health Research fellowship.",
year = "2002",
month = sep,
day = "20",
doi = "10.1016/S0092-8674(02)00969-8",
language = "English",
volume = "110",
pages = "737--749",
journal = "Cell",
issn = "0092-8674",
number = "6",
}