A novel and essential mechanism determining specificity and activity of protein phosphatase 2A (PP2A) in vivo

被引：87

作者：

Fellner, T ^{[1
]}

Lackner, DH ^{[1
]}

Hombauer, H ^{[1
]}

Piribauer, P ^{[1
]}

Mudrak, I ^{[1
]}

Zaragoza, K ^{[1
]}

Juno, C ^{[1
]}

Ogris, E ^{[1
]}

机构：

[1] Univ Vienna, Vienna Bioctr, Inst Med Biochem, Div Mol Biol, A-1030 Vienna, Austria

来源：

GENES & DEVELOPMENT | 2003年 / 17卷 / 17期

关键词：

PP2A biogenesis; PTPA; metals; active site;

D O I：

10.1101/gad.259903

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：2138 / 2150

页数：13

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