Fig. 1.

Diagrammatic representation of the signalling pathways activated in the unfolded protein response following ER stress. The sensor molecules, PKR-like endoplasmic reticulum kinase (PERK), inositol-requiring 1 (Ire1) and activating transcription factor 6 (ATF6), are transmembrane proteins normally held inactive by the binding of GRP78/BiP, but are released when the GRP78 preferentially binds to misfolded proteins accumulating in the ER lumen. The UPR aims to restore homeostasis within the ER, but there are also links to the inflammatory response through the Ire1 pathway and TNF receptor-associated factor 2 (TRAF2).