| Literature DB >> 12297047 |
Michael A Crackower1, Gavin Y Oudit, Ivona Kozieradzki, Renu Sarao, Hui Sun, Takehiko Sasaki, Emilio Hirsch, Akira Suzuki, Tetsuo Shioi, Junko Irie-Sasaki, Rajan Sah, Hai-Ying M Cheng, Vitalyi O Rybin, Giuseppe Lembo, Luigi Fratta, Antonio J Oliveira-dos-Santos, Jeffery L Benovic, C Ronald Kahn, Seigo Izumo, Susan F Steinberg, Matthias P Wymann, Peter H Backx, Josef M Penninger.
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. PI3Kalpha mediates the alteration in cell size while PI3Kgamma acts as a negative regulator of cardiac contractility. Mechanistically, PI3Kgamma 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-PI3Kgamma pathway in the modulation of heart muscle contractility.Entities:
Mesh：
Substances：
Year: 2002 PMID： 12297047 DOI： 10.1016/s0092-8674(02)00969-8
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582