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

• Published in: Genes & development Vol. 17; no. 17; pp. 2138 - 2150
• Main Authors: Fellner, Thomas, Lackner, Daniel H, Hombauer, Hans, Piribauer, Patrick, Mudrak, Ingrid, Zaragoza, Katrin, Juno, Claudia, Ogris, Egon
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01-09-2003
• Subjects: 3T3 Cells; Animals; Apoptosis - physiology; Binding Sites; HeLa Cells; Humans; Metals - metabolism; Mice; Mutation; Phosphoprotein Phosphatases - genetics; Phosphoprotein Phosphatases - metabolism; Protein Phosphatase 2; Research Papers; RNA Interference - physiology; Substrate Specificity - genetics
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.259903

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.