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. 1999 Jan 21;397(6716):271-4.
doi: 10.1038/16729.

Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase

H P Harding  1 , Y Zhang, D Ron
Affiliations

Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase

H P Harding et al. Nature. .

Erratum in

  • Nature 1999 Mar 4;398(6722):90

Abstract

Protein synthesis and the folding of the newly synthesized proteins into the correct three-dimensional structure are coupled in cellular compartments of the exocytosis pathway by a process that modulates the phosphorylation level of eukaryotic initiation factor-2alpha (eIF2alpha) in response to a stress signal from the endoplasmic reticulum (ER). Activation of this process leads to reduced rates of initiation of protein translation during ER stress. Here we describe the cloning of perk, a gene encoding a type I transmembrane ER-resident protein. PERK has a lumenal domain that is similar to the ER-stress-sensing lumenal domain of the ER-resident kinase Ire1, and a cytoplasmic portion that contains a protein-kinase domain most similar to that of the known eIF2alpha kinases, PKR and HRI. ER stress increases PERK's protein-kinase activity and PERK phosphorylates eIF2alpha on serine residue 51, inhibiting translation of messenger RNA into protein. These properties implicate PERK in a signalling pathway that attenuates protein translation in response to ER stress.

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Comment in

  • Translational control perks up.
    Silverman RH, Williams BR. Silverman RH, et al. Nature. 1999 Jan 21;397(6716):208-9, 211. doi: 10.1038/16586. Nature. 1999. PMID: 9930691 No abstract available.

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