ArticleThe Journal of biological chemistry2010
Protein kinase C-induced phosphorylation of Orai1 regulates the intracellular Ca2+ level via the store-operated Ca2+ channel.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
81 citing papers in PubMed, 134 citations in OpenAlex.
- Density of functional Ca2+ release-activated Ca2+ (CRAC) channels declines after T-cell activation.Channels (Austin, Tex.)Trial
- A Quartet of Native Orai Channel Isoforms Orchestrates Graded NFAT Activation and Transcription.bioRxiv : the preprint server for biology · 2026Article
- Identifying 2PHDO as a SOCE Inhibitor from Chinese Herbal Extracts.Current pharmaceutical biotechnology · 2026Article
- Calcium Signaling Dysregulation in Diabetic Cardiomyopathy: Roles of STIM and Orai Channels.Handbook of experimental pharmacology · 2026Review
- Store-operated calcium entry-based targets for novel cancer therapeutic development.The Journal of pharmacology and experimental therapeutics · 2025Review
- A subset of Orai1α and Orai1β subunits heteromerizes to form CRAC channels.Cell communication and signaling : CCS · 2025Article
- Suppressed ORAI1-STIM1-dependent CaThe Journal of biological chemistry · 2024Article
- Differential functional role of Orai1 variants in constitutive CaThe Journal of biological chemistry · 2024Article
- Non-voltage-gated CaAmerican journal of physiology. Renal physiology · 2024Review
- ORAI CaBiomolecules · 2024Review
- Review
- Ion channels and channelopathies in glomeruli.Physiological reviews · 2023Review
- Store-Operated Calcium Entry in Breast Cancer Cells Is Insensitive to Orai1 and STIM1 N-Linked Glycosylation.Cancers · 2022Article
- CRAC and SK Channels: Their Molecular Mechanisms Associated with Cancer Cell Development.Cancers · 2022Review
- Similarities and Differences between the Orai1 Variants: Orai1α and Orai1β.International journal of molecular sciences · 2022Review
- Store-Operated CaCancers · 2022Article
- Article
- Control of STIM and Orai function by post-translational modifications.Cell calcium · 2022Review
- SPLUNC1 is a negative regulator of the Orai1 CaPhysiological reports · 2022Article
- PKC-β modulates CaGenes & genomics · 2022Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Ca(2+) signals through store-operated Ca(2+) (SOC) channels, activated by the depletion of Ca(2+) from the endoplasmic reticulum, regulate various physiological events. Orai1 is the pore-forming subunit of the Ca(2+) release-activated Ca(2+) (CRAC) channel, the best characterized SOC channel. Orai1 is activated by stromal interaction molecule (STIM) 1, a Ca(2+) sensor located in the endoplasmic reticulum. Orai1 and STIM1 are crucial for SOC channel activation, but the molecular mechanisms regulating Orai1 function are not fully understood. In this study, we demonstrate that protein kinase C (PKC) suppresses store-operated Ca(2+) entry (SOCE) by phosphorylation of Orai1. PKC inhibitors and knockdown of PKCbeta both resulted in increased Ca(2+) influx. Orai1 is strongly phosphorylated by PKC in vitro and in vivo at N-terminal Ser-27 and Ser-30 residues. Consistent with these results, substitution of endogenous Orai1 with an Orai1 S27A/S30A mutant resulted in increased SOCE and CRAC channel currents. We propose that PKC suppresses SOCE and CRAC channel function by phosphorylation of Orai1 at N-terminal serine residues Ser-27 and Ser-30.
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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.