There are four known mammalian protein kinases that phosphorylate eIF2α, including PKR-like ER kinase (PERK, EIF2AK3), heme-regulated eIF2α kinase (HRI, EIF2AK1), general control non-depressible 2 (GCN2, EIF2AK4) and double stranded RNA dependent protein kinase (PKR, EIF2AK2).