Signaling pathway of GRP78

Signaling pathway of GRP78. Upon ER stress, GRP78 separates from UPR sensors (PERK, IRE1 and ATF6) and preferentially associates with unfolded proteins, upon which UPR is activated. These sensors elicit damage control pathways synergistically, activated partially by ATFs (ATF4 and ATF6). The nuclear form ATFs subsequently act on ERSE, increasing the expression of GRP78. Overexpressed GRP78 may be redistributed to the cell surface by means of vesicle transport, recognizing extracellular ligands and activating PI3K/AKT and MAPK signaling pathways. The activation of PI3K/AKT and MAPK signaling pathways may also lead to the rapid induction of GRP78. GRP, glucose-regulated protein; ER, endoplasmic reticulum; UPR, unfolded protein response; PERK, protein kinase-like ER kinase; IRE1, inositol-requiring enzyme 1; ATF, activating transcription factor; ERSE, endoplasmic reticulum stress-response element; PI3 K, phosphoinositide 3-kinase; AKT, protein kinase B; MAPK, mitogen-activated protein kinase; MHC, major histocompatibility complex; Par-4, prostate apoptosis response-4.

Publication

Endoplasmic reticulum chaperone glucose-regulated protein 78 in gastric cancer: An emerging biomarker. (2018) Yan Wang, et al. Oncol Lett. 2018 May;15(5):6087-6093. Figure: F1. All organisms Caenorhabditis elegans Homo sapiens

Disease mentions