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.
Identification of the macromolecular complex responsible for PI3Kγ-dependent regulation of cAMP levels
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A. Perino, A. Ghigo, F. Damilano, E. Hirsch; Identification of the macromolecular complex responsible for PI3Kγ-dependent regulation of cAMP levels. Biochem Soc Trans 1 August 2006; 34 (4): 502–503. doi: https://doi.org/10.1042/BST0340502
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