Protein kinase RNA-activated (PKR)

Protein kinase RNA-activated (PKR) is an interferon-inducible serine/threonine protein kinase encoded by the EIF2AK2 gene. It is activated primarily by binding double-stranded RNA (dsRNA), which often arises during viral infection. Upon activation—either by dsRNA or cellular activators like PACT—PKR dimerizes and autophosphorylates, becoming catalytically active. Its main substrate is the alpha subunit of eukaryotic initiation factor 2 (eIF2α); phosphorylation at Ser51 leads to global inhibition of mRNA translation, blocking both viral and host protein synthesis as an antiviral defense mechanism. Beyond its canonical antiviral role, PKR participates in regulating apoptosis through death receptor pathways involving FADD/caspases and direct p53 phosphorylation; it also modulates inflammatory signaling via NF-kB pathway activation and influences various mitogen-activated kinases involved in inflammation and stress responses. Dysregulation has been implicated in cancer biology due to roles in controlling cell growth/proliferation/apoptosis balance; it may function as a tumor suppressor under some conditions. PKR’s broad involvement across innate immunity makes it a key node for therapeutic intervention but also raises challenges regarding specificity/safety if targeted pharmacologically.

Other names

Interferon-induced double-stranded RNA-activated protein kinaseEukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2)Protein kinase R

Drugs or molecules targeting PKR would typically act by inhibiting its activation/phosphorylation activity, thereby preventing downstream effects such as inhibition of protein synthesis or induction of apoptosis. Viral proteins can also inhibit PKR to evade host immunity; for example, influenza virus uses p58IPK to block PKR-mediated eIF2α phosphorylation.