PKR dimer autophosphorylates

Stable Identifier
R-HSA-9833820
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Human cytomegalovirus
Compartment
cytosol
ReviewStatus
5/5
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PKR dimer autophosphorylates
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Control of protein translation via phosphorylation of eIF-2a requires a high-level of PKR (EIF2AK2) kinase activity resulting from PKR autophosphorylation on at least 11 serine, tyrosine, and threonine residues. Thus, PKR has both serine/threonine and tyrosine kinase activities (Meurs et al, 1990; Romano et al, 1998; Taylor et al, 2001; Zhang et al, 2001; Dar et al, 2005; Dey et al, 2005; Su et al, 2006; Wang et al, 2017; Cesaro et al, 2021). Autophosphorylation takes place both intramolecularly ("cis") and intermolecularly ("trans") (Thomis & Samuel, 1993).
Literature References
PubMed ID Title Journal Year
11337501 Binding of double-stranded RNA to protein kinase PKR is required for dimerization and promotes critical autophosphorylation events in the activation loop

Dever, TE, Tian, B, Hinnebusch, AG, Romano, PR, Mathews, MB, Zhang, F, Nagamura-Inoue, T, Ozato, K

J Biol Chem 2001
9528799 Autophosphorylation in the activation loop is required for full kinase activity in vivo of human and yeast eukaryotic initiation factor 2alpha kinases PKR and GCN2

Herring, C, Wang, Q, Zhang, X, Hinnebusch, AG, Romano, PR, Garcia-Barrio, MT, Mathews, MB, Zhang, F, Qin, J, Taylor, DR

Mol. Cell. Biol. 1998
16179258 Higher-order substrate recognition of eIF2alpha by the RNA-dependent protein kinase PKR

Sicheri, F, Dever, TE, Dar, AC

Cell 2005
28281686 Auto-phosphorylation Represses Protein Kinase R Activity

Williams, BR, Wang, D, Willard, B, Polekhina, G, de Weerd, NA, Sadler, AJ

Sci Rep 2017
16179259 Mechanistic link between PKR dimerization, autophosphorylation, and eIF2alpha substrate recognition

Dey, M, Ozato, K, Cao, C, Dever, TE, Sicheri, F, Tamura, T, Dar, AC

Cell 2005
11152499 Hepatitis C virus envelope protein E2 does not inhibit PKR by simple competition with autophosphorylation sites in the RNA-binding domain

Lai, MM, Tian, B, Hinnebusch, AG, Romano, PR, Mathews, MB, Taylor, DR

J Virol 2001
33911136 PKR activity modulation by phosphomimetic mutations of serine residues located three aminoacids upstream of double-stranded RNA binding motifs

Borghese, F, Michiels, T, Wavreil, F, Vertommen, D, Hayashi, Y, Cesaro, T

Sci Rep 2021
1695551 Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon

Hovanessian, AG, Thomas, NS, Williams, BR, Galabru, J, Meurs, E, Kerr, IM, Chong, K

Cell 1990
7693978 Mechanism of interferon action: evidence for intermolecular autophosphorylation and autoactivation of the interferon-induced, RNA-dependent protein kinase PKR

Samuel, CE, Thomis, DC

J Virol 1993
16373505 Tyrosine phosphorylation acts as a molecular switch to full-scale activation of the eIF2alpha RNA-dependent protein kinase

Su, Q, Baltzis, D, Qu, LK, Wong, AH, Koromilas, AE, Wang, S

Proc Natl Acad Sci U S A 2006
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein kinase activity of EIF2AK2 dimer [cytosol]

Physical Entity
EIF2AK2 dimer [cytosol] (Homo sapiens)
Activity
protein kinase activity (GO:0004672)
This event is regulated
Negatively by
Regulator
TRS1 [cytosol] (Human cytomegalovirus)
Authored
Stephan, R  (2023-05-03)
Reviewed
Patel, RC  (2023-08-16)
Created
Stephan, R  (2023-05-04)
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