PI3Kgamma 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, PI3Kgamma acts as a negative modulator of contractility, by decreasing cAMP concentration through a kinase-independent mechanism. Indeed, whereas PI3Kgamma-deficient mice show an abnormal cAMP elevation, cAMP levels in knock-in mouse mutants, expressing a kinase-dead PI3Kgamma, are comparable with wild-type controls. PI3Kgamma regulates cardiac cAMP homoeostasis by forming a macromolecular complex containing PDE3B (phosphodiesterase 3B). In this complex, PI3Kgamma could regulate PDE3B activity through protein kinase A, a PDE activator.

Identification of the macromolecular complex responsible for PI3Kgamma-dependent regulation of cAMP levels.

PERINO, Alessia;GHIGO, Alessandra;DAMILANO, Federico;HIRSCH, Emilio
2006

Abstract

PI3Kgamma 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, PI3Kgamma acts as a negative modulator of contractility, by decreasing cAMP concentration through a kinase-independent mechanism. Indeed, whereas PI3Kgamma-deficient mice show an abnormal cAMP elevation, cAMP levels in knock-in mouse mutants, expressing a kinase-dead PI3Kgamma, are comparable with wild-type controls. PI3Kgamma regulates cardiac cAMP homoeostasis by forming a macromolecular complex containing PDE3B (phosphodiesterase 3B). In this complex, PI3Kgamma could regulate PDE3B activity through protein kinase A, a PDE activator.
34(Pt 4)
502
503
http://www.biochemsoctrans.org/bst/034/0502/0340502.pdf
cAMP; compartmentalization; heart failure; phosphodiesterase 3B (PDE3B); phosphoinositide 3-kinase g (PI3Kg); signal transduction.
PERINO A; GHIGO A; DAMILANO F; HIRSCH E
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/35051
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