Evolution of eIF2α Kinases: Adapting Translational Control to Diverse Stresses

  • Stefan Rothenburg
  • Millie M. Georgiadis
  • Ronald C. WekEmail author


An important mechanism regulating protein synthesis involves phosphorylation of the α subunit of eukaryotic initiation factor-2 (eIF2α). In response to a range of environmental and physiological stresses, phosphorylation of eIF2α prevents this initiation factor from appropriately delivering initiator methionyl tRNA to the translation machinery. As a consequence there is lowered translation, which helps cells conserve energy and resources and better adapt to the underlying stress. During evolution, new eIF2α kinases arose by adjoining new combinations of stress-sensing regions to the kinase catalytic domain, culminating in their activation in response to different sets of stress conditions. The physiological traits of the organism and the nature of the environmental stress, along with the activating properties of each eIF2α kinase, help determine the nature and number of eIF2α kinases expressed in a given organism. This review will highlight current perspectives on the phylogenetic relationships between eIF2α kinases, the central structural and functional roles of their regulatory domains in the mechanisms regulating translational control, and how these eIF2α kinase family members evolved for optimal organism adaptation to stress.


Kinase Domain Unfold Protein Response Myxoma Virus Kinase Catalytic Domain Grass Carp Reovirus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors acknowledge support by NIH grant GM049164 (RCW and MMG) and AI114851 (SR) and the Grace M. Showalter Research Trust Fund (RCW).


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Stefan Rothenburg
    • 1
  • Millie M. Georgiadis
    • 2
  • Ronald C. Wek
    • 2
    Email author
  1. 1.Laboratory for Host-Specific Virology, Division of BiologyKansas State UniversityManhattanUSA
  2. 2.Department of Biochemistry and Molecular BiologyIndiana University School of MedicineIndianapolisUSA

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