Reactome | EIF2AK3 (PERK) phosphorylates EIF2S1 (eIF2-alpha)Phosphorylation of eIF2-alpha by PERK

EIF2AK3 (PERK) phosphorylates EIF2S1 (eIF2-alpha)Phosphorylation of eIF2-alpha by PERK

Stable Identifier

R-HSA-381111

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, endoplasmic reticulum membrane

ReviewStatus

5/5

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EIF2AK3 (PERK) phosphorylates EIF2S1 (eIF2-alpha)Phosphorylation of eIF2-alpha by PERK

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The C-terminal domain of PERK (EIF2AK3) has kinase activity when PERK homodimerizes. PERK kinase specifically phosphorylates Ser52 of eIF2-alpha, causing an arrest in translation. The result is that translation of ER-targeted proteins is halted on ribosomes in the vicinity of activated PERK. The general arrest of translation results in the loss of short-lived proteins such as Cyclin D1, causing an arrest of the cell cycle in G1.

Literature References

PubMed ID	Title	Journal	Year
10026192	Characterization of a mutant pancreatic eIF-2alpha kinase, PEK, and co-localization with somatostatin in islet delta cells An, J, Shi, Y, Hayes, SE, Yang, NN, Sandusky, GE, Stramm, LE, Liang, J	J Biol Chem	1999
17956313	PERK in the life and death of the pancreatic beta-cell Herbert, TP	Biochem Soc Trans	2007
16288713	Interaction of recombinant human eIF2 subunits with eIF2B and eIF2alpha kinases Suragani, RN, Ehtesham, NZ, Kamindla, R, Ramaiah, KV	Biochem Biophys Res Commun	2005
18664456	Polycystin-2 down-regulates cell proliferation via promoting PERK-dependent phosphorylation of eIF2alpha Li, Q, Wang, Z, Tang, Y, Chen, XZ, Yang, J, Liang, G	Hum Mol Genet	2008
11907036	Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stress Wek, RC, Vattem, KM, Ma, K	J Biol Chem	2002
12370288	Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha Koromilas, A, Wouters, BG, Diehl, A, Rastani, S, Koumenis, C, Naczki, C, Sonenberg, N, Koritzinsky, M	Mol Cell Biol	2002