| Autor: |
Blake-Hodek KA; Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA., Williams BC, Zhao Y, Castilho PV, Chen W, Mao Y, Yamamoto TM, Goldberg ML |
| Jazyk: |
angličtina |
| Zdroj: |
Molecular and cellular biology [Mol Cell Biol] 2012 Apr; Vol. 32 (8), pp. 1337-53. Date of Electronic Publication: 2012 Feb 21. |
| DOI: |
10.1128/MCB.06525-11 |
| Abstrakt: |
The atypical AGC kinase Greatwall (Gwl) mediates a pathway that prevents the precocious removal of phosphorylations added to target proteins by M phase-promoting factor (MPF); Gwl is thus essential for M phase entry and maintenance. Gwl itself is activated by M phase-specific phosphorylations that are investigated here. Many phosphorylations are nonessential, being located within a long nonconserved region, any part of which can be deleted without effect. Using mass spectrometry and mutagenesis, we have identified 3 phosphorylation sites (phosphosites) critical to Gwl activation (pT193, pT206, and pS883 in Xenopus laevis) located in evolutionarily conserved domains that differentiate Gwl from related kinases. We propose a model in which the initiating event for Gwl activation is phosphorylation by MPF of the proline-directed sites T193 and T206 in the presumptive activation loop. After this priming step, Gwl can intramolecularly phosphorylate its C-terminal tail at pS883; this site probably plays a role similar to that of the tail/Z motif of other AGC kinases. These events largely (but not completely) explain the full activation of Gwl at M phase. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
