A novel and essential mechanism determining specificity and activity of protein phosphatase 2A (PP2A) in vivo.
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.
Mesh Terms:
3T3 Cells, Animals, Apoptosis, Binding Sites, Hela Cells, Humans, Metals, Mice, Mutation, Phosphoprotein Phosphatases, Protein Phosphatase 2, RNA Interference, Substrate Specificity
3T3 Cells, Animals, Apoptosis, Binding Sites, Hela Cells, Humans, Metals, Mice, Mutation, Phosphoprotein Phosphatases, Protein Phosphatase 2, RNA Interference, Substrate Specificity
Genes Dev.
Date: Sep. 01, 2003
PubMed ID: 12952889
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