ArticleMolecular biology of the cell2004
Nck-dependent activation of extracellular signal-regulated kinase-1 and regulation of cell survival during endoplasmic reticulum stress.
Article in Molecular biology of the cell, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 170 citations in OpenAlex.
- ER Stress Is Associated with a "Mesenchymal Drift" in an Anaplastic Thyroid Carcinoma Cell Line.Cancers · 2025Article
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Inhibition of IRE1α/XBP1 axis alleviates LPS-induced acute lung injury by suppressing TXNIP/NLRP3 inflammasome activation and ERK/p65 signaling pathway.Respiratory research · 2024Article
- Redox regulation of UPR signalling and mitochondrial ER contact sites.Cellular and molecular life sciences : CMLS · 2024Review
- Exploring the IRE1 interactome: From canonical signaling functions to unexpected roles.The Journal of biological chemistry · 2024Review
- IRE1 RNase controls CD95-mediated cell death.EMBO reports · 2024Article
- SIRT7 orchestrates melanoma progression by simultaneously promoting cell survival and immune evasion via UPR activation.Signal transduction and targeted therapy · 2023Article
- Calnexin, More Than Just a Molecular Chaperone.Cells · 2023Review
- Review
- IRE1/XBP1 and endoplasmic reticulum signaling - from basic to translational research for cardiovascular disease.Current opinion in physiology · 2022Article
- Stress-induced inflammation evoked by immunogenic cell death is blunted by the IRE1α kinase inhibitor KIRA6 through HSP60 targeting.Cell death and differentiation · 2022Article
- Activation of farnesoid X receptor suppresses ER stress and inflammationFrontiers in nutrition · 2022Article
- Nck adaptors at a glance.Journal of cell science · 2021Article
- IRE1α RIDD activity induced under ER stress drives neuronal death by the degradation of 14-3-3 θ mRNA in cortical neurons during glucose deprivation.Cell death discovery · 2021Article
- Manipulation of IRE1-Dependent MAPK Signaling by a Vibrio Agonist-Antagonist Effector Pair.mSystems · 2021Article
- Endoplasmic reticulum stress signals in the tumour and its microenvironment.Nature reviews. Cancer · 2021Review
- Sinner or Saint?: Nck Adaptor Proteins in Vascular Biology.Frontiers in cell and developmental biology · 2021Review
- Inositol Requiring Enzyme (IRE), a multiplayer in sensing endoplasmic reticulum stress.Animal cells and systems · 2021Review
- Unraveling the Molecular Nexus between GPCRs, ERS, and EMT.Mediators of inflammation · 2021Review
- Endoplasmic reticulum stress induces hepatic plasminogen activator inhibitor 1 in murine nonalcoholic steatohepatitis.FASEB bioAdvances · 2020Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In response to stress, the endoplasmic reticulum (ER) signaling machinery triggers the inhibition of protein synthesis and up-regulation of genes whose products are involved in protein folding, cell cycle exit, and/or apoptosis. We demonstrate that the misfolding agents azetidine-2-carboxylic acid (Azc) and tunicamycin initiate signaling from the ER, resulting in the activation of Jun-N-terminal kinase, p44(MAPK)/extracellular signal-regulated kinase-1 (ERK-1), and p38(MAPK) through IRE1alpha-dependent mechanisms. To characterize the ER proximal signaling events involved, immuno-isolated ER membranes from rat fibroblasts treated with ER stress inducers were used to reconstitute the activation of the stress-activated protein kinase/mitogen-activate protein kinase (MAPK) pathways in vitro. This allowed us to demonstrate a role for the SH2/SH3 domain containing adaptor Nck in ERK-1 activation after Azc treatment. We also show both in vitro and in vivo that under basal conditions ER-associated Nck represses ERK-1 activation and that upon ER stress this pool of Nck dissociates from the ER membrane to allow ERK-1 activation. Moreover, under the same conditions, Nck-null cells elicit a stronger ERK-1 activation in response to Azc stress, thus, correlating with an enhanced survival phenotype. These data delineate a novel mechanism for the regulation of ER stress signaling to the MAPK pathway and demonstrate a critical role for Nck in ER stress and cell survival.
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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.