Eukaryotic Translation Initiation Factor 2 Alpha Kinase 3 (EIF2aK3)

Phosphorylation of eIF2-alpha results in inhibition of the guanine nucleotide exchange factor eIF-2B, thereby reducing the rate of the GDP to GTP exchange that is required for eIF2 to carry out additional rounds of translation initiation. The eukaryotic eIF2-alpha kinases PKR, HRI, and yeast GCN2 share extensive homology within their catalytic domains, but have distinct regulatory domains allowing for different physiologic signals to regulate phosphorylation of eIF2-alpha.The kinase domain of human PEK is similar to that of the other eIF2-alpha kinases, but the 550-residue N-terminal region is unique, perhaps reflecting the different physiologic signals that regulate its activity. Like rat PEK, recombinant human PEK was autophosphorylated and specifically phosphorylated eIF2-alpha.