title: A novel and essential mechanism determining specificity and activity of protein phosphatase 2A (PP2A) in vivo.
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.
authors.affiliation: Institute of Medical Biochemistry, Division of Molecular Biology, Vienna Biocenter, University of Vienna, A-1030 Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fellner
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Lackner
authors.forename: Hans
authors.initials: H
authors.lastname: Hombauer
authors.forename: Patrick
authors.initials: P
authors.lastname: Piribauer
authors.forename: Ingrid
authors.initials: I
authors.lastname: Mudrak
authors.forename: Katrin
authors.initials: K
authors.lastname: Zaragoza
authors.forename: Claudia
authors.initials: C
authors.lastname: Juno
authors.forename: Egon
authors.initials: E
authors.lastname: Ogris
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001665:Binding Sites; D006367:HeLa Cells; D006801:Humans; D008670:Metals / Q000378:metabolism; D051379:Mice; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D054648:Protein Phosphatase 2; D034622:RNA Interference / Q000502:physiology; D013379:Substrate Specificity / Q000235:genetics
chemical_list: D008670:Metals; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2