Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
Bioessays. 2013 Jul;35(7):602-11. doi: 10.1002/bies.201200176.
Class I PI 3-kinases signal by producing the signaling lipid phosphatidylinositol(3,4,5) trisphosphate, which in turn acts by recruiting downstream effectors that contain specific lipid-binding domains. The class I PI 3-kinases comprise four distinct catalytic subunits linked to one of seven different regulatory subunits. All the class I PI 3-kinases produce the same signaling lipid, PIP3, and the different isoforms have overlapping expression patterns and are coupled to overlapping sets of upstream activators. Nonetheless, studies in cultured cells and in animals have demonstrated that the different isoforms are coupled to distinct ranges of downstream responses. This review focuses on the mechanisms by which the production of a common product, PIP3, can produce isoform-specific signaling by PI 3-kinases.
I 类 PI3-激酶通过产生信号脂质磷脂酰肌醇（3,4,5）三磷酸（PIP3）来发挥作用，PIP3 进而通过募集含有特定脂质结合域的下游效应物来发挥作用。I 类 PI3-激酶由四个不同的催化亚基与七个不同的调节亚基之一相连。所有的 I 类 PI3-激酶都产生相同的信号脂质 PIP3，不同的同工型具有重叠的表达模式，并与重叠的上游激活剂结合。尽管如此，在培养细胞和动物中的研究表明，不同的同工型与不同范围的下游反应相关联。这篇综述的重点是 I 类 PI3-激酶产生共同产物 PIP3 的机制如何产生同工型特异性信号。
