The regulation of class IA PI 3-kinases by inter-subunit interactions.
The regulation of class IA PI 3-kinases by inter-subunit interactions.
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DOI：
10.1007/82_2010_52
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发表时间：
2010
影响因子：
--
通讯作者：
Backer, Jonathan M.
中科院分区：
文献类型：
--
作者：
Backer, Jonathan M.
磷酸肌醇 3-激酶 (PI 3-激酶) 由生长因子和激素受体激活，调节细胞生长、存活、运动和对营养条件变化的反应。 PI 3-激酶根据其亚基组成及其对磷酸肌醇的底物特异性进行分类。 IA 类 PI 3 激酶是一种异二聚体，由一个调节亚基（p85α、p85β、p55α、p50α 或 p55γ）和一个 110 kDa 催化亚基（p110α、β 或 δ）组成。 IB 类 PI 3 激酶也是一种二聚体，由一个调节亚基（p101 或 p87）和一个催化亚基（p110γ）组成。 I 类酶将利用 PI、PI[4]P 或 PI[4,5]P2 作为体外底物，但被认为主要在细胞中产生 PI[3,4,5]P3。 IB类PI 3激酶催化亚基p110γ的晶体结构于1999年得到解决，并且IA类p110α催化亚基和IA类p85α调节亚基的所有单独结构域的晶体或NMR结构也已得到解决。然而，完整的 PI 3 激酶的结构仍然难以捉摸。尽管如此，过去十年的研究已经对生理条件下酶的调节方式产生了重要的见解。本章将具体讨论 IA 类 PI 3 激酶活性的调节，重点关注 p85 和 p110 亚基之间的调节相互作用以及生理激活剂和致癌突变对这些相互作用的调节。 IA 类 PI 3 激酶下游的复杂信号网络将在本卷的其他章节中讨论。
Phosphoinositide 3-kinases (PI 3-kinases) are activated by growth factor and hormone receptors, and regulate cell growth, survival, motility, and responses to changes in nutritional conditions. PI 3-kinases have been classified according to their subunit composition and their substrate specificity for phosphoinositides. The class IA PI 3-kinase is a heterodimer consisting of one regulatory subunit (p85α, p85β, p55α, p50α, or p55γ) and one 110-kDa catalytic subunit (p110α, β or δ). The Class IB PI 3-kinase is also a dimer, composed of one regulatory subunit (p101 or p87) and one catalytic subunit (p110γ). Class I enzymes will utilize PI, PI[4]P, or PI[4,5]P2 as substrates in vitro, but are thought to primarily produce PI[3,4,5]P3 in cells. The crystal structure of the Class IB PI 3-kinase catalytic subunit p110γ was solved in 1999, and crystal or NMR structures of the Class IA p110α catalytic subunit and all of the individual domains of the Class IA p85α regulatory subunit have been solved. However, a structure of an intact PI 3-kinase enzyme has remained elusive. In spite of this, studies over the past 10 years have lead to important insights into how the enzyme is regulated under physiological conditions. This chapter will specifically discuss the regulation of Class IA PI 3-kinase enzymatic activity, focusing on regulatory interactions between the p85 and p110 subunits and the modulation of these interactions by physiological activators and oncogenic mutations. The complex web of signaling downstream from Class IA PI 3-kinases will be discussed in other chapters in this volume.
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影响因子：
2.7
作者：
Bernadó, P;de la Torre, JG;Pons, M
通讯作者：
Pons, M
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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通讯作者：
Hirsch E
影响因子：
64.8
作者：
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通讯作者：
Thomson, Elizabeth