PKR; a sentinel kinase for cellular stress

The double stranded RNA (dsRNA)-activated protein kinase PKR is a ubiquitou sly expressed serine/threonine protein kinase that is induced by interferon and activated by dsRNA, cytokine, growth factor and stress signals, It is essential for cells to respond adequately to different stresses including g rowth factor deprivation, products of the inflammatory response (TNF) and b acterial (lipopolysaccharide) and viral (dsRNA) products. As a vital compon ent of the cellular antiviral response pathway, PKR is autophosphorylated a nd activated an binding to dsRNA. This results in inhibition of protein syn thesis via the phosphorylation of eIF2 alpha and also induces transcription of inflammatory genes by PKR-dependent signaling of the activation of diff erent transcription factors. Along with RNaseL, PKR constitutes the antivir al arm of a group of mammalian stress response proteins that have counterpa rts in yeast. What began as adaptation to amino acid deprivation and sensin g unfolded proteins in the endoplasmic reticulum has evolved into a family of sophisticated mammalian stress response proteins able to mediate cellula r responses to both physical and biological stress.