Identification of the macromolecular complex responsible for PI3Kγ-dependent regulation of cAMP levels. (21st July 2006)

• Record Type: Journal Article
• Authors: Perino, A.; Ghigo, A.; Damilano, F.; Hirsch, E.
• Is Part Of: Biochemical Society transactions. Volume 34:Number 4(2006)
• Page Start: 502
• Page End: 503
• Publication Date: 2006-07-21
• Subjects: cAMP -- compartmentalization -- heart failure -- phosphodiesterase 3B (PDE3B) -- phosphoinositide 3-kinase γ (PI3Kγ) -- signal transduction; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST0340502
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : 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.