PKR - Mediating cellular stress responses through multiple signaling pathways

Thu, 09/10/2015 - 14:29

Protein kinase R (PKR) is an intracellular stress-sensing protein that is able to detect and respond to viral infections. While PKR is able to sense and respond to a variety of signals, dsRNA is a well-characterized ligand. dsRNA produced during viral replication binds to PKR and induces a conformational change, dimerization, and exposure of the catalytic autophosphorylation site (1). Once in this active form PKR is able to phosphorylate substrates to regulate cell growth and stress responses. The most well characterized PKR substrate is the eukaryotic translation initiation factor EIF2A. Phosphorylation of this substrate blocks protein synthesis by preventing the recycling of EIF2A during translation (1). In addition to viral induced cellular stress, PKR senses and responds to bacterial infections, general ER stress, and inflammation by modulating transcriptional responses (2). These responses are carried out through interactions with a variety of cell signaling pathways including p53, MAPK, STAT, and NF-kB (2). PKR also seems to be an important regulator of cell growth and differentiation as mutations can lead to cell transformation and tumorigenesis (2).

Studies of PKR functions have important implications in cancer, microbiology, and neuroscience research. Through the examination of PKR induction and PKR protein interactions with PKR antibodies investigators are able to better understand responses to a variety of cell stresses. Through western blotting with the PKR antibody Fang et al. characterized the interaction between palmitate and PKR (3). This interaction inhibits PKR activation and can enhance apoptosis. In a separate study, investigators measured PKR phosphorylation in response to palmitate using a phospho-specific PKR antibody (4). This study showed palmitate acts through multiple pathways to regulate apoptosis through the expression of ATF4. PKR has also been used as a test case to examine the effective design of siRNA constructs to silence endogenous genes. Western blots with the PKR antibody were used as a readouts to evaluate the effectiveness of the siRNA design algorithm (5). PKR induction can be used as a tool to block mRNA translation in vivo. Jiang et al. expressed PKR in hippocampal neurons to selectively block protein synthesis and examine the effect on memory formation (6). PKR expression was monitored through western blots with the PKR antibody and through qPCR in an attempt to identify the role of translation regulation in memory formation.

Novus Biologicals offers PKR reagents for your research needs including:


  1. 10557102
  2. 17158706
  3. 24862841
  4. 23339444
  5. 24393396
  6. 20164343

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