title: Greatwall phosphorylates an inhibitor of protein phosphatase 2A that is essential for mitosis.
abstract: Entry into mitosis in eukaryotes requires the activity of cyclin-dependent kinase 1 (Cdk1). Cdk1 is opposed by protein phosphatases in two ways: They inhibit activation of Cdk1 by dephosphorylating the protein kinases Wee1 and Myt1 and the protein phosphatase Cdc25 (key regulators of Cdk1), and they also antagonize Cdk1's own phosphorylation of downstream targets. A particular form of protein phosphatase 2A (PP2A) containing a B55δ subunit (PP2A- B55δ) is the major protein phosphatase that acts on model CDK substrates in Xenopus egg extracts and has antimitotic activity. The activity of PP2A-B55δ is high in interphase and low in mitosis, exactly opposite that of Cdk1. We report that inhibition of PP2A-B55δ results from a small protein, known as α-endosulfine (Ensa), that is phosphorylated in mitosis by the protein kinase Greatwall (Gwl). This converts Ensa into a potent and specific inhibitor of PP2A-B55δ. This pathway represents a previously unknown element in the control of mitosis.
authors.affiliation: Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.
authors.forename: Satoru
authors.initials: S
authors.lastname: Mochida
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Maslen
authors.forename: Mark
authors.initials: M
authors.lastname: Skehel
authors.forename: Tim
authors.initials: T
authors.lastname: Hunt
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D036341:Intercellular Signaling Peptides and Proteins; D007399:Interphase; D008938:Mitosis; D050505:Mutant Proteins / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D050505:Mutant Proteins; D010455:Peptides; D010750:Phosphoproteins; D029867:Xenopus Proteins; C064321:cyclic AMP-regulated phosphoprotein 19; C075663:endosulfine; D012694:Serine; C544010:MASTL protein, Xenopus; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D054648:Protein Phosphatase 2