Identification of the macromolecular complex responsible for PI3Kγ-dependent regulation of cAMP levels
Copyright policy )Identification of the macromolecular complex responsible for PI3Kγ-dependent regulation of cAMP levels
PI3Kγ is a phosphoinositide 3-kinase characterized by both lipid and protein kinase activity. It is activated by G-protein-coupled receptors and is predominantly expressed in leucocytes; in addition, recent work showed its presence in the heart and its involvement in regulating cardiac functions. In this tissue, PI3Kγ acts as a negative modulator of contractility, by decreasing cAMP concentration through a kinase-independent mechanism. Indeed, whereas PI3Kγ-deficient mice show an abnormal cAMP elevation, cAMP levels in knock-in mouse mutants, expressing a kinase-dead PI3Kγ, are comparable with wild-type controls. PI3Kγ regulates cardiac cAMP homoeostasis by forming a macromolecular complex containing PDE3B (phosphodiesterase 3B). In this complex, PI3Kγ could regulate PDE3B activity through protein kinase A, a PDE activator.
- University of Turin Italy
Isoenzymes, Phosphatidylinositol 3-Kinases, cAMP; compartmentalization; heart failure; phosphodiesterase 3B (PDE3B); phosphoinositide 3-kinase g (PI3Kg); signal transduction., Myocardium, Cyclic AMP, Animals, Class Ib Phosphatidylinositol 3-Kinase, Humans, Protein Binding, Signal Transduction
Isoenzymes, Phosphatidylinositol 3-Kinases, cAMP; compartmentalization; heart failure; phosphodiesterase 3B (PDE3B); phosphoinositide 3-kinase g (PI3Kg); signal transduction., Myocardium, Cyclic AMP, Animals, Class Ib Phosphatidylinositol 3-Kinase, Humans, Protein Binding, Signal Transduction
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