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Greatwall-phosphorylated Endosulfine is Both an Inhibitor and a Substrate of PP2A-B55 Heterotrimers
| العنوان: | Greatwall-phosphorylated Endosulfine is Both an Inhibitor and a Substrate of PP2A-B55 Heterotrimers |
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| المؤلفون: | Williams, Byron C., Filter, Joshua J., Blake-Hodek, Kristina A., Wadzinski, Brian E., Fuda, Nicholas J., Shalloway, David, Goldberg, Michael L. |
| سنة النشر: | 2014 |
| المجموعة: | Quantitative Biology |
| مصطلحات موضوعية: | Quantitative Biology - Subcellular Processes, Quantitative Biology - Molecular Networks |
| الوصف: | 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. Comment: 65 pages of text, 11 figures, 10 supplementary figures. This paper will be published in the journal eLife |
| نوع الوثيقة: | Working Paper |
| URL الوصول: | http://arxiv.org/abs/1402.4063 |
| رقم الانضمام: | edsarx.1402.4063 |
| قاعدة البيانات: | arXiv |
| الوصف غير متاح. |