摘要

The phosphorylation of the subunit a of eukaryotic translation initiation factor 2 (eIF2 alpha), a critical regulatory event in controlling protein translation, has recently been found to mediate the induction of autophagy. However, the mediators of autophagy downstream of eIF2 alpha remain unknown. Here, we provide evidence that eIF2 alpha phosphorylation is required for phosphorylation of eukaryotic elongation factor 2 (eEF-2) during nutrient starvation. In addition, we show that eukaryotic elongation factor 2 kinase (eEF-2K) is also required for autophagy signaling during ER stress, suggesting that phosphorylation of eEF-2 may serve as an integrator of various cell stresses for autophagy signaling. On the other hand, although the activation of eEF-2K in response to starvation requires the phosphorylation of eIF2 alpha, additional pathways relying partly on Ca(2 ) flux may control eEF-2K activity during ER stress, as eIF2 alpha phosphorylation is dispensable for both eEF-2 phosphorylation and autophagy in this context.

  • 出版日期2009-4-1