ArticleThe Journal of biological chemistry2016
T Cell Receptor-induced Nuclear Factor κB (NF-κB) Signaling and Transcriptional Activation Are Regulated by STIM1- and Orai1-mediated Calcium Entry.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 78 citations in OpenAlex.
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- Unremitting pro-inflammatory T-cell phenotypes, and macrophage activity, following paediatric burn injury.Clinical & translational immunology · 2024Article
- Multifaceted control of T cell differentiation by STIM1.Trends in biochemical sciences · 2023Review
- NFAT1 and NFκB regulates expression of the common γ-chain cytokine receptor in activated T cells.Cell communication and signaling : CCS · 2023Article
- Astrocyte reactivity and inflammation-induced depression-like behaviors are regulated by Orai1 calcium channels.Nature communications · 2023Article
- Transcriptomic dissection of termite gut microbiota following entomopathogenic fungal infection.Frontiers in physiology · 2023Article
- Bivalent binding of staphylococcal superantigens to the TCR and CD28 triggers inflammatory signals independently of antigen presenting cells.Frontiers in immunology · 2023Article
- Pharmacologic modulation of intracellular NaProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Toll-like receptor 4 activation enhances Orai1-mediated calcium signal promoting cytokine production in spinal astrocytes.Cell calcium · 2022Article
- ORAI1-Regulated Gene Expression in Breast Cancer Cells: Roles for STIM1 Binding, Calcium Influx and Transcription Factor Translocation.International journal of molecular sciences · 2022Article
- Fluid shear stress enhances T cell activation through Piezo1.BMC biology · 2022Article
- Cardiomyocyte stromal interaction molecule 1 is a key regulator of CaPhysiological reports · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
T cell activation following antigen binding to the T cell receptor (TCR) involves the mobilization of intracellular Ca(2+) to activate the key transcription factors nuclear factor of activated T lymphocytes (NFAT) and NF-κB. The mechanism of NFAT activation by Ca(2+) has been determined. However, the role of Ca(2+) in controlling NF-κB signaling is poorly understood, and the source of Ca(2+) required for NF-κB activation is unknown. We demonstrate that TCR- but not TNF-induced NF-κB signaling upstream of IκB kinase activation absolutely requires the influx of extracellular Ca(2+) via STIM1-dependent Ca(2+) release-activated Ca(2+)/Orai channels. We further show that Ca(2+) influx controls phosphorylation of the NF-κB protein p65 on Ser-536 and that this posttranslational modification controls its nuclear localization and transcriptional activation. Notably, our data reveal that this role for Ca(2+) is entirely separate from its upstream control of IκBα degradation, thereby identifying a novel Ca(2+)-dependent distal step in TCR-induced NF-κB activation. Finally, we demonstrate that this control of distal signaling occurs via Ca(2+)-dependent PKCα-mediated phosphorylation of p65. Thus, we establish the source of Ca(2+) required for TCR-induced NF-κB activation and define a new distal Ca(2+)-dependent checkpoint in TCR-induced NF-κB signaling that has broad implications for the control of immune cell development and T cell functional specificity.
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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.