PKR activation by dsRNA. Long dsRNA, shRNA, or pre-miRNA can activate protein kinase R (PKR) via binding to the dsRNA binding motifs, causing a conformational change, dimerization, and autophosphorylation. Activated PKR can inhibit protein synthesis by phosphorylation of translational initiation factor eIF2α. PKR can also function as a signal-transducing kinase interacting with IκB kinase (IKK) and p38 mitogen-activated protein kinase (p38) regulating gene transcription by activation of different transcription factors including NFκB and ATF2.