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Mol Cell Biol. April 1, 2012; 32 (8): 1337-53.

Determinants for activation of the atypical AGC kinase Greatwall during M phase entry.

Blake-Hodek KA , Williams BC , Zhao Y , Castilho PV , Chen W , Mao Y , Yamamoto TM , Goldberg ML .

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.

PubMed ID: 22354989
PMC ID: PMC3318580
Article link: Mol Cell Biol.
Grant support: GM048430 NIGMS NIH HHS , R01 GM048430 NIGMS NIH HHS

Genes referenced: mastl

External Resources:

Adams, 2003, Pubmed[+]

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