Janssens V, Goris J
Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Herestraat 49, B-3000 Leuven, Belgium.
Biochem J. 2001 Feb 1;353(Pt 3):417-39. doi: 10.1042/0264-6021:3530417.
Protein phosphatase 2A (PP2A) comprises a family of serine/threonine phosphatases, minimally containing a well conserved catalytic subunit, the activity of which is highly regulated. Regulation is accomplished mainly by members of a family of regulatory subunits, which determine the substrate specificity, (sub)cellular localization and catalytic activity of the PP2A holoenzymes. Moreover, the catalytic subunit is subject to two types of post-translational modification, phosphorylation and methylation, which are also thought to be important regulatory devices. The regulatory ability of PTPA (PTPase activator), originally identified as a protein stimulating the phosphotyrosine phosphatase activity of PP2A, will also be discussed, alongside the other regulatory inputs. The use of specific PP2A inhibitors and molecular genetics in yeast, Drosophila and mice has revealed roles for PP2A in cell cycle regulation, cell morphology and development. PP2A also plays a prominent role in the regulation of specific signal transduction cascades, as witnessed by its presence in a number of macromolecular signalling modules, where it is often found in association with other phosphatases and kinases. Additionally, PP2A interacts with a substantial number of other cellular and viral proteins, which are PP2A substrates, target PP2A to different subcellular compartments or affect enzyme activity. Finally, the de-regulation of PP2A in some specific pathologies will be touched upon.
蛋白磷酸酶2A(PP2A)是一个丝氨酸/苏氨酸磷酸酶家族,至少包含一个高度保守的催化亚基,其活性受到高度调控。这种调控主要由一个调节亚基家族的成员来完成,这些调节亚基决定了PP2A全酶的底物特异性、(亚)细胞定位和催化活性。此外,催化亚基还会经历两种类型的翻译后修饰,即磷酸化和甲基化,这也被认为是重要的调控机制。最初被鉴定为一种刺激PP2A磷酸酪氨酸磷酸酶活性的蛋白质的PTPA(蛋白酪氨酸磷酸酶激活剂)的调节能力,以及其他调节输入也将被讨论。在酵母、果蝇和小鼠中使用特定的PP2A抑制剂和分子遗传学方法,已经揭示了PP2A在细胞周期调控、细胞形态和发育中的作用。PP2A在特定信号转导级联反应的调节中也起着重要作用,这一点从它存在于许多大分子信号模块中就可以看出,在这些模块中它经常与其他磷酸酶和激酶结合在一起。此外,PP2A与大量其他细胞和病毒蛋白相互作用,这些蛋白是PP2A的底物,将PP2A靶向不同的亚细胞区室或影响酶的活性。最后,将涉及PP2A在某些特定病理状态下的失调情况。