Protein kinase RNA-activated (EIF2AK2) (PKR)

Protein kinase RNA-activated (PKR), encoded by the EIF2AK2 gene, is a critical serine/threonine kinase that functions as a sentinel in the innate immune system by detecting viral double-stranded RNA (dsRNA) (UniProt P19544). Upon activation, PKR phosphorylates the alpha subunit of eukaryotic initiation factor 2 (eIF2-alpha), which halts global protein synthesis and prevents viral replication within the host cell (NCBI Gene ID: 7315). In many malignancies, particularly those driven by oncogenic Ras mutations, this antiviral pathway is disrupted. Activated Ras signaling pathways, such as the MEK/ERK cascade, can inhibit PKR activation or neutralize its downstream effects, rendering these tumor cells susceptible to viral infection (Coffey et al., Science, 1998; Strong et al., EMBO J, 1998). This specific molecular defect is the therapeutic basis for oncolytic viruses like Reovirus (Pelareorep), which selectively replicate in and destroy Ras-activated tumor cells while sparing normal cells with an intact PKR response. Consequently, the PKR pathway serves as both a biological barrier to infection and a targetable vulnerability in Ras-driven cancers.

Other names

EIF2AK2Eukaryotic translation initiation factor 2-alpha kinase 2PRKRInterferon-induced, double-stranded RNA-activated protein kinasep68 kinase

Exploitation of defective PKR signaling in Ras-transformed cells to allow selective oncolytic viral replication and subsequent tumor cell lysis.