Protein Kinase RNA-activated (PKR) is a crucial enzyme in the human body, encoded by the EIF2AK2 gene on chromosome 2 . It is a serine/threonine kinase that plays a significant role in the cellular response to viral infections and other stress signals. PKR is activated by double-stranded RNA (dsRNA), which is often produced during viral replication. This activation leads to the phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2α), resulting in the inhibition of protein synthesis and the suppression of viral replication .
PKR is primarily activated by binding to dsRNA, which induces its autophosphorylation and subsequent activation. Once activated, PKR phosphorylates eIF2α, leading to a reduction in protein synthesis. This mechanism is a part of the cell’s antiviral defense, as it helps to limit the production of viral proteins . Additionally, PKR can interact with other cellular proteins, such as PACT (Protein Activator of the Interferon-induced Protein Kinase), which further modulates its activity .
PKR plays a pivotal role in the cellular response to viral infections. For instance, during HIV-1 replication, PKR is transiently activated, leading to the phosphorylation of eIF2α and a decrease in viral protein synthesis . However, HIV-1 has evolved mechanisms to counteract this response. The virus can modulate the activity of PKR through various viral and cellular factors, including the interaction with PACT and ADAR1 (Adenosine Deaminase Acting on RNA), which can inhibit PKR activity and promote viral replication .
Given its crucial role in the antiviral response, PKR is a potential target for therapeutic interventions. Modulating PKR activity could enhance the body’s ability to fight viral infections. For example, enhancing PKR activation could improve the antiviral response, while inhibiting PKR could be beneficial in conditions where excessive PKR activity leads to detrimental effects, such as in certain inflammatory diseases .