| Autor: |
Williams BC; Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States., Filter JJ, Blake-Hodek KA, Wadzinski BE, Fuda NJ, Shalloway D, Goldberg ML |
| Jazyk: |
angličtina |
| Zdroj: |
ELife [Elife] 2014 Mar 11; Vol. 3, pp. e01695. Date of Electronic Publication: 2014 Mar 11. |
| DOI: |
10.7554/eLife.01695 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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