Protein kinase R
protein-coding gene in the species Homo sapiens
Protein kinase RNA-activated also known as protein kinase R (PKR), interferon-induced, double-stranded RNA-activated protein kinase, or eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) is an enzyme that in humans is encoded by the EIF2AK2 gene on chromosome 2. PKR is a serine/tyrosine kinase that is 551 amino acids long.
PKR is inducible by various mechanisms of stress and protects against viral infections. It also has a role in several signaling pathways.
Mechanism of action
Protein kinase-R is activated by double-stranded RNA (dsRNA), introduced to the cells by a viral infection. In situations of viral infection, the dsRNA created by viral replication and gene expression binds to the N-terminal domain, activating the protein. PKR activation via dsRNA is length dependent, requiring the dsRNA to be 30 bp in length to bind to PKR molecules. However, excess dsRNA can diminish activation of PKR. Binding to dsRNA is believed to activate PKR by inducing dimerization of the kinase domains and subsequent auto-phosphorylation reactions. It is not yet established whether PKR activates in cis, with a protomer's activation loop reaching into its own catalytic site, or in trans, with the activation loop being phosphorylated in a face to face geometry by a conjugate protomer. PKR can also be activated by the protein PACT via phosphorylation of S287 on its M3 domain.
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