Eukaryotic elongation factor 2 kinase (eEF-2K) is an atypical calcium/calmodulin-dependent protein kinase (CaMK-III) that is known to modulate protein synthesis through the inhibitory phosphorylation of elongation factor 2.  eEF-2K has been suggested to promote cancer cell proliferation, invasion and survival.  Despite its pivotal role in translation regulation and potential role in tumorigenesis, the mechanism of eEF-2K activation has not been described in detail.  In vitro analysis of eEF-2K autophosphorylation indicates that in the presence of calcium/calmodulin, robust phosphorylation of Thr-348 occurs within seconds of adding MgATP.  Mutagenesis studies suggest that Thr-348 phosphorylation is required for substrate phosphorylation, but not self-phosphorylation.  Phosphorylation of Ser-500 lags behind the phosphorylation of Thr-348, and confers calcium-independent activity to eEF-2K.  Surprisingly, this calcium-independent activity requires the presence of calmodulin.  Autophosphorylation of eEF-2K could be a significant mechanism for its dynamic regulation, especially upon the influx of calcium during cellular signaling events.

Autophosphorylation regulates the activity and calcium-dependence of eukaryotic elongation factor 2 kinase

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.