Perking up protein synthesis.(Left) Phosphorylation of eIF2α by PERK in response to unfolded proteins in the ER inhibits translation initiation and protein synthesis in pancreatic β cells. This results in a decrease in the number of unfolded proteins in the ER and promotion of β cell survival. eIF2α phosphorylation also results in the transcriptional activation of genes that are important for cell survival.(Right) Control of glucose production (gluconeogenesis) in the liver by eIF2α phosphorylation may be mediated by GCN2 because deletion of the other eIF2α kinases (including PERK) does not result in hypoglycemia. eIF2α phosphorylation may increase the synthesis of gluconeogenic enzymes (such as PEPCK) or of transcription factors that activate the expression of their genes.