负责PI3Kγ依赖性调节cAMP水平的大分子复合物的鉴定。

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

作者信息

Perino A, Ghigo A, Damilano F, Hirsch E

机构信息

Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 5bis, 10126 Torino, Italy.

出版信息

Biochem Soc Trans. 2006 Aug;34(Pt 4):502-3. doi: 10.1042/BST0340502.

DOI:10.1042/BST0340502

PMID:16856844

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.

摘要

PI3Kγ是一种磷酸肌醇3激酶，具有脂质激酶和蛋白激酶活性。它由G蛋白偶联受体激活，主要在白细胞中表达；此外，最近的研究表明它存在于心脏中，并参与调节心脏功能。在该组织中，PI3Kγ通过一种不依赖激酶的机制降低cAMP浓度，从而作为收缩力的负调节因子。实际上，PI3Kγ缺陷小鼠表现出cAMP异常升高，而表达激酶失活的PI3Kγ的敲入小鼠突变体中的cAMP水平与野生型对照相当。PI3Kγ通过形成包含磷酸二酯酶3B（PDE3B）的大分子复合物来调节心脏cAMP稳态。在这个复合物中，PI3Kγ可以通过蛋白激酶A（一种PDE激活剂）来调节PDE3B的活性。