title: Greatwall-phosphorylated Endosulfine is both an inhibitor and a substrate of PP2A-B55 heterotrimers.
abstract: During M phase, Endosulfine (Endos) family proteins are phosphorylated by Greatwall kinase (Gwl), and the resultant pEndos inhibits the phosphatase PP2A-B55, which would otherwise prematurely reverse many CDK-driven phosphorylations. We show here that PP2A-B55 is the enzyme responsible for dephosphorylating pEndos during M phase exit. The kinetic parameters for PP2A-B55's action on pEndos are orders of magnitude lower than those for CDK-phosphorylated substrates, suggesting a simple model for PP2A-B55 regulation that we call inhibition by unfair competition. As the name suggests, during M phase PP2A-B55's attention is diverted to pEndos, which binds much more avidly and is dephosphorylated more slowly than other substrates. When Gwl is inactivated during the M phase-to-interphase transition, the dynamic balance changes: pEndos dephosphorylated by PP2A-B55 cannot be replaced, so the phosphatase can refocus its attention on CDK-phosphorylated substrates. This mechanism explains simultaneously how PP2A-B55 and Gwl together regulate pEndos, and how pEndos controls PP2A-B55. DOI: http://dx.doi.org/10.7554/eLife.01695.001.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
authors.forename: Byron C
authors.initials: BC
authors.lastname: Williams
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Filter
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Blake-Hodek
authors.forename: Brian E
authors.initials: BE
authors.lastname: Wadzinski
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Fuda
authors.forename: David
authors.initials: D
authors.lastname: Shalloway
authors.forename: Michael L
authors.initials: ML
authors.lastname: Goldberg
mesh_terms: D002453:Cell Cycle; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C075663:endosulfine; C490167:Gwl protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases; C079898:tws protein, Drosophila
keywords: M phase exit; cell cycle; kinases; phosphatases