Regulation of Greatwall kinase during Xenopus oocyte maturation
| Autor: | James L. Maller, Byron C. Williams, Michael L. Goldberg, Andrea L. Lewellyn, Kristina A. Blake-Hodek, Tomomi M. Yamamoto |
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| Rok vydání: | 2011 |
| Předmět: |
G2 Phase
Xenopus Phosphatase Protein Serine-Threonine Kinases Xenopus Proteins 03 medical and health sciences 0302 clinical medicine Cyclin-dependent kinase Phosphoprotein Phosphatases medicine Animals Protein Phosphatase 2 Phosphorylation Kinase activity Molecular Biology Progesterone 030304 developmental biology 0303 health sciences biology Kinase Cell Cycle Articles Cell Biology Protein phosphatase 2 biology.organism_classification Oocyte Cyclin-Dependent Kinases Cell biology medicine.anatomical_structure Biochemistry Mutation Oocytes biology.protein Intercellular Signaling Peptides and Proteins Female Peptides Cell Division 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Greatwall kinase is required for M phase maintenance by inhibiting PP2A. Gwl associates with PP2A in G2 oocytes, but the complex dissociates during M phase (meiosis I). Mutating Lys71 to Met (K71M) generates gain-of-function Gwl kinase activity toward endosulfinethat is sufficient to induce oocyte maturation in the absence of progesterone. Greatwall kinase has been identified as a key element in M phase initiation and maintenance in Drosophila, Xenopus oocytes/eggs, and mammalian cells. In M phase, Greatwall phosphorylates endosulfine and related proteins that bind to and inhibit protein phosphatase 2A/B55, the principal phosphatase for Cdk-phosphorylated substrates. We show that Greatwall binds active PP2A/B55 in G2 phase oocytes but dissociates from it when progesterone-treated oocytes reach M phase. This dissociation does not require Greatwall kinase activity or phosphorylation at T748 in the presumptive T loop of the kinase. A mutant K71M Greatwall, also known as Scant in Drosophila, induces M phase in the absence of progesterone when expressed in oocytes, despite its reduced stability and elevated degradation by the proteasome. M phase induction by Scant Greatwall requires protein synthesis but is not associated with altered binding or release of PP2A/B55 as compared to wild-type Greatwall. However, in vitro studies with Greatwall proteins purified from interphase cells indicate that Scant, but not wild-type Greatwall, has low but detectable activity against endosulfine. These results demonstrate progesterone-dependent regulation of the PP2A/B55–Greatwall interaction during oocyte maturation and suggest that the cognate Scant Greatwall mutation has sufficient constitutive kinase activity to promote M phase in Xenopus oocytes. |
| Databáze: | OpenAIRE |
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