p-PKR dimer phosphorylates eIF2-alpha

Stable Identifier
R-HSA-9835885
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Human respiratory syncytial virus A, Human cytomegalovirus
Compartment
cytosol
ReviewStatus
5/5
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p-PKR dimer phosphorylates eIF2-alpha
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Protein kinase R (PKR, EIF2AK2) must dimerize and autophosphorylate in order to become activated and subsequently phosphorylate translation initiation factor eIF2 subunit alpha (eIF2alpha, EIF2S1) at S51 (Dar et al, 2005). As a result, eIF2 forms a complex with its own guanine nucleotide exchange factor, eIF2B, which inhibits the recycling of GTP for GDP on eIF2 (reviewed in Dever, 2002). eIF2alpha phosphorylation by PKR is sufficient to induce apoptosis (Scheuner et al, 2006). The resulting inhibition of protein translation is not complete, however, as many transcripts involved in the stress response are not affected or are even preferentially translated by mechanisms involving upstream open reading frames (uORFs) (reviewed by Wek, 2018).
Literature References
PubMed ID Title Journal Year
29440070 Role of eIF2α Kinases in Translational Control and Adaptation to Cellular Stress

Wek, RC

Cold Spring Harb Perspect Biol 2018
11909525 Gene-specific regulation by general translation factors

Dever, TE

Cell 2002
16179258 Higher-order substrate recognition of eIF2alpha by the RNA-dependent protein kinase PKR

Dar, AC, Dever, TE, Sicheri, F

Cell 2005
16717090 Double-stranded RNA-dependent protein kinase phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2 mediates apoptosis

Scheuner, D, Patel, R, Wang, F, Lee, K, Kumar, K, Wu, J, Nilsson, A, Karin, M, Kaufman, RJ

J Biol Chem 2006
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein kinase activity of p-EIF2AK2 dimer [cytosol]

Physical Entity
p-EIF2AK2 dimer [cytosol] (Homo sapiens)
Activity
protein kinase activity (GO:0004672)
This event is regulated
Negatively by
Regulator
TRS1 [cytosol] (Human cytomegalovirus)
Regulator
Protein N decamer [cytosol] (Human respiratory syncytial virus A)
Authored
Stephan, R  (2023-05-15)
Reviewed
Patel, RC  (2023-08-16)
Created
Stephan, R  (2023-05-22)
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