| First Author | Harding HP | Year | 1999 |
| Journal | Nature | Volume | 397 |
| Issue | 6716 | Pages | 271-4 |
| PubMed ID | 9930704 | Mgi Jnum | J:51759 |
| Mgi Id | MGI:1333015 | Doi | 10.1038/16729 |
| Citation | Harding HP, et al. (1999) Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase [published erratum appears in Nature 1999 Mar 4;398(6722):90] [see comments]. Nature 397(6716):271-4 |
| abstractText | 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. |
