一种在体内决定蛋白磷酸酶2A（PP2A）特异性和活性的全新且关键的机制。
A novel and essential mechanism determining specificity and activity of protein phosphatase 2A (PP2A) in vivo.
作者信息
Fellner Thomas, Lackner Daniel H, Hombauer Hans, Piribauer Patrick, Mudrak Ingrid, Zaragoza Katrin, Juno Claudia, Ogris Egon
机构信息
Institute of Medical Biochemistry, Division of Molecular Biology, Vienna Biocenter, University of Vienna, A-1030 Vienna, Austria.
出版信息
Genes Dev. 2003 Sep 1;17(17):2138-50. doi: 10.1101/gad.259903.
Abstract
Protein phosphatase 2A (PP2A) is an essential intracellular serine/threonine phosphatase containing a catalytic subunit that possesses the potential to dephosphorylate promiscuously tyrosine-phosphorylated substrates in vitro. How PP2A acquires its intracellular specificity and activity for serine/threonine-phosphorylated substrates is unknown. Here we report a novel and phylogenetically conserved mechanism to generate active phospho-serine/threonine-specific PP2A in vivo. Phosphotyrosyl phosphatase activator (PTPA), a protein of so far unknown intracellular function, is required for the biogenesis of active and specific PP2A. Deletion of the yeast PTPA homologs generated a PP2A catalytic subunit with a conformation different from the wild-type enzyme, as indicated by its altered substrate specificity, reduced protein stability, and metal dependence. Complementation and RNA-interference experiments showed that PTPA fulfills an essential function conserved from yeast to man.
摘要
蛋白磷酸酶2A（PP2A）是一种重要的细胞内丝氨酸/苏氨酸磷酸酶，它含有一个催化亚基，该催化亚基在体外具有对酪氨酸磷酸化底物进行随意去磷酸化的潜力。PP2A如何获得其对丝氨酸/苏氨酸磷酸化底物的细胞内特异性和活性尚不清楚。在此，我们报告了一种在体内产生有活性的磷酸丝氨酸/苏氨酸特异性PP2A的新的且系统发育保守的机制。磷酸酪氨酸磷酸酶激活剂（PTPA）是一种迄今细胞内功能未知的蛋白质，它是活性和特异性PP2A生物合成所必需的。酵母PTPA同源物的缺失产生了一种PP2A催化亚基，其构象与野生型酶不同，这表现为其底物特异性改变、蛋白质稳定性降低以及对金属的依赖性。互补和RNA干扰实验表明，PTPA履行了从酵母到人类保守的基本功能。
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