FIG. 2.

Protein kinase-mediated phosphorylation of eIF2α and additional downstream targets of p-eIF2α and IRE1α. (A) Phosphorylation of eIF2α can be mediated by four protein kinases: double-stranded RNA-activated protein kinase (PKR), general control nonderepressible 2 kinase (Gcn2), heme-regulated inhibitor kinase (HRI), and PERK. Phosphorylation of eIF2α is linked to the inflammatory response via activation of nuclear factor kappa-β (NFκβ). PERK-mediated phosphorylation of nuclear erythroid 2 p45-related factor 2 (Nrf2) links PERK activation to the regulation of redox balance (see text). (B) Activation of IRE1α can lead to activation of stress kinases, including p38 mitogen-activated protein kinase (MAPK), extracellular-regulated kinase (ERK), c-Jun-NH₂-terminal kinase (JNK), and NFκβ (see text).