ArticlePloS one2010
Targeted mutation of the mouse Grp94 gene disrupts development and perturbs endoplasmic reticulum stress signaling.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 81 citations in OpenAlex.
- Expanding roles of N-glycosylation in the endoplasmic reticulum.Trends in cell biology · 2026Review
- GRP94 is indispensable for definitive endoderm specification of human induced pluripotent stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Role of HSP90 in Type 2 Diabetes Mellitus and Its Association with Liver Diseases.Molecular biotechnology · 2025Review
- TRIB3 mediates vascular calcification by facilitating self-ubiquitination and dissociation of Smurf1 in chronic kidney disease.The Journal of clinical investigation · 2025Article
- [High-resolution Differential Proteomic Analysis of Mouse Secondary Oocytes and First Polar Bodies].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Endoplasmic reticulum stress signaling modulates ischemia/reperfusion injury in the aged heart by regulating mitochondrial maintenance.Molecular medicine (Cambridge, Mass.) · 2024Review
- GRP94 is an IGF-1R chaperone and regulates beta cell death in diabetes.Cell death & disease · 2024Article
- Insulin secretion deficits in a Prader-Willi syndrome β-cell model are associated with a concerted downregulation of multiple endoplasmic reticulum chaperones.PLoS genetics · 2023Article
- A proinsulin-dependent interaction between ENPL-1 and ASNA-1 in neurons is required to maintain insulin secretion in C. elegans.Development (Cambridge, England) · 2023Article
- GRP94 Inhabits the Immortalized Porcine Hepatic Stellate Cells Apoptosis under Endoplasmic Reticulum Stress through Modulating the Expression of IGF-1 and Ubiquitin.International journal of molecular sciences · 2022Article
- The biology and inhibition of glucose-regulated protein 94/gp96.Medicinal research reviews · 2022Review
- Active nNOS Is Required for Grp94-Induced Antioxidant Cytoprotection: A Lesson from Myogenic to Cancer Cells.International journal of molecular sciences · 2022Article
- Nitric oxide-targeted protein phosphorylation during human sperm capacitation.Scientific reports · 2021Article
- Article
- Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases.Nature reviews. Cardiology · 2021Review
- Autophagy stimulation reduces ocular hypertension in a murine glaucoma model via autophagic degradation of mutant myocilin.JCI insight · 2021Article
- The loss-of-function PCSK9Q152H variant increases ER chaperones GRP78 and GRP94 and protects against liver injury.The Journal of clinical investigation · 2021Article
- ENPL-1, theDevelopment (Cambridge, England) · 2020Article
- Article
- GRP94 regulates M1 macrophage polarization and insulin resistance.American journal of physiology. Endocrinology and metabolism · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
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Abstract
Glucose-regulated protein 94 (GRP94) is one of the most abundant endoplasmic reticulum (ER) resident proteins and is the ER counterpart of the cytoplasmic heat shock protein 90 (HSP90). GRP94, a component of the GRP78 chaperone system in protein processing, has pro-survival properties with implicated function in cancer progression and autoimmune disease. Previous studies on the loss of GRP94 function showed that it is required for embryonic development, regulation of toll-like receptors and innate immunity of macrophages. Here we report the creation of mouse models targeting exon 2 of the Grp94 allele that allows both traditional and conditional knockout (KO) of Grp94. In this study, we utilized the viable Grp94+/+ and +/- mice, as well as primary mouse embryonic fibroblasts generated from them as experimental tools to study its role in ER chaperone balance and ER stress signaling. Our studies reveal that while Grp94 heterozygosity reduces GRP94 level it does not alter ER chaperone levels or the ER stress response. To study the effect of complete loss of GRP94 function, since homozygous GRP94 KO leads to embryonic lethality, we generated Grp94-/- embryonic stem cells. In contrast to Grp94 heterozygosity, complete knockout of GRP94 leads to compensatory upregulation of the ER chaperones GRP78, calnexin and calreticulin but not protein disulphide isomerase. Unexpectedly, loss of GRP94 leads to significant decrease in the level of ER-stress induced spliced form of XBP-1 protein, a downstream target of the IRE1 signaling pathway. Furthermore, from analysis of microarray database and immunohistochemical staining, we present predictions where GRP94 may play an important role in specific adult organ homeostasis and function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.