The mosquito Anopheles gambiae has three distinct enzymes (HRI, PERK and GCN2) while Drosophila melanogaster and Caenorhabditis elegans have only two (PERK and GCN2) [ 8].
ER stress is sensed by three distinct ER sensory proteins, PERK, ATF6 and IRE-1, which are kept inactivated by binding with ER-resident chaperones such as GRP78 and GRP94.
Such an interaction with BiP ATPase domain is novel, and suggests that the BiPATPase domain interaction with Ire1 or Perk is distinct from the classical chaperone-substrate interaction, and may serve some key signaling functions that we set out to elucidate.
The UPR is mediated by three distinct ER-localized transmembrane proteins: PERK, IRE1 and ATF6.
ER stress signaling pathways involve three distinct stress sensor proteins, IRE1, PERK, and ATF6.
Strikingly, IRE1α and PERK hyperphosphorylation patterns were distinct (Figure 1A), reflecting various levels of phosphorylation upon activation.
In mammals, the UPR is transduced by three distinct classes of ER transmembrane proteins: PERK, ATF6 and Ire1p homologues [ 27].
The role of quantitative differences in the pERK response leading to distinct cellular outcomes is well characterized in PC12 neurons (Marshall, 1995), and the transcriptional response to the proliferative program mediated by sustained pERK activation in 3T3 fibroblasts has been reported (Yamamoto et al., 2006).
30 demonstrating that ROS is an important genomic response to ER stress and is characterized by the activation of three distinct signal transduction pathways mediated by PERK, IRE1 and ATF6.
In metazoa, distinct stress conditions activate different eIF2α kinases (PERK, PKR, GCN2, and HRI) that converge on phosphorylating a unique serine in eIF2α.
There are already three mechanistically distinct pathways, mediated by IRE1, ATF6 and PERK respectively, known to operate in parallel to activate UPR in mammalians [ 36].
