Eukaryotic translation initiation factor 2-alpha kinase 2 (PKR) (PKR)

Eukaryotic translation initiation factor 2-alpha kinase 2 (PKR) is an interferon-induced serine/threonine kinase that serves as a critical sensor in the innate immune system [1, 11]. It is primarily activated by double-stranded RNA (dsRNA), a common intermediate in viral replication, which triggers its dimerization and autophosphorylation [1, 5]. Once active, PKR phosphorylates the alpha subunit of eukaryotic initiation factor 2 (eIF2-alpha), leading to a global inhibition of protein synthesis to halt viral production [2, 16]. Beyond its antiviral role, PKR is involved in various signaling pathways, including NF-kappaB and MAPK, which regulate inflammation and apoptosis [1, 13]. Dysregulation of PKR activity is linked to several pathologies, including neurodegenerative diseases like Alzheimer's and Parkinson's, where chronic activation contributes to neuronal death [7, 12]. It also plays a role in metabolic disorders such as diabetes and obesity by contributing to the metaflammasome and insulin resistance [1, 11]. In oncology, PKR can act as a tumor suppressor by inducing apoptosis, though its role can be complex and context-dependent [6, 15]. Therapeutic strategies involve small-molecule inhibitors to treat neurodegeneration and inflammation, or activators to enhance antitumor and antiviral responses [7, 8].

Other names

Protein kinase REIF2AK2PRKRp68 kinaseP1/eIF-2A protein kinaseInterferon-inducible eIF2-alpha kinaseDYT33LEUDEN

PKR modulators act by either inhibiting the kinase's autophosphorylation and subsequent eIF2-alpha phosphorylation to prevent protein synthesis shutdown, or by activating the kinase to induce apoptosis and inflammatory signaling in viral or malignant cells [7, 8, 12].