Protein Kinase R (PKR)

Protein kinase R (PKR) is a serine/threonine protein kinase that plays a central role in the cellular response to stress, particularly viral infection. It is an intracellular sensor primarily activated by double-stranded RNA (dsRNA), which is often produced during viral replication. PKR is inducible by various stress mechanisms and participates in several signaling pathways related to immunity, inflammation, apoptosis, and cell regulation. Activation typically requires binding of dsRNA; this promotes dimerization and autophosphorylation of the kinase domains. Main substrate: eukaryotic translation initiation factor eIF2α. Phosphorylation leads to global suppression of mRNA translation. Chronic activation implicated in neurological diseases, traumatic brain injury, aging-related pathologies, tumorigenesis, neurodegenerative diseases, and certain movement disorders like dystonia. PKR activity must be tightly regulated due to its broad effects on survival versus death decisions within cells.

Other names

EIF2AK2

Phosphorylation of eIF2α, leading to inhibition of translation initiation