{"doi":"10.1016/j.jbc.2023.105310","title":"A multiple-oscillator mechanism underlies antigen-induced Ca2+ oscillations in Jurkat T-cells","abstract":"T-cell receptor stimulation triggers cytosolic Ca 2+ signaling by inositol-1,4,5-trisphosphate (IP 3 )-mediated Ca 2+ release from the endoplasmic reticulum (ER) and Ca 2+ entry through Ca 2+ release-activated Ca 2+ (CRAC) channels gated by ER-located stromal-interacting molecules (STIM1/2). Physiologically, cytosolic Ca 2+ signaling manifests as regenerative Ca 2+ oscillations, which are critical for nuclear factor of activated T-cells-mediated transcription. In most cells, Ca 2+ oscillations are thought to originate from IP 3 receptor-mediated Ca 2+ release, with CRAC channels indirectly sustaining them through ER refilling. Here, experimental and computational evidence support a multiple-oscillator mechanism in Jurkat T-cells whereby both IP 3 receptor and CRAC channel activities oscillate and directly fuel antigen-evoked Ca 2+ oscillations, with the CRAC channel being the major contributor. KO of either STIM1 or STIM2 significantly reduces CRAC channel activity. As such, STIM1 and STIM2 synergize for optimal Ca 2+ oscillations and activation of nuclear factor of activated T-cells 1 and are essential for ER refilling. The loss of both STIM proteins abrogates CRAC channel activity, drastically reduces ER Ca 2+ content, severely hampers cell proliferation and enhances cell death. These results clarify the mechanism and the contribution of STIM proteins to Ca 2+ oscillations in T-cells.","journal":"Journal of Biological Chemistry","year":2023,"id":341690,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9438,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1078239,"name":"Olivier Romito","orcid":null,"position":1,"is_corresponding":false},{"id":656428,"name":"Ahmed Emam Abdelnaby","orcid":"0000-0003-4775-3643","position":2,"is_corresponding":false},{"id":264987,"name":"Ping Xin","orcid":null,"position":3,"is_corresponding":false},{"id":656426,"name":"Trayambak Pathak","orcid":"0000-0002-0719-2995","position":4,"is_corresponding":false},{"id":1077692,"name":"S. Weir","orcid":"0000-0003-2256-0263","position":5,"is_corresponding":false},{"id":416452,"name":"Vivien Kirk","orcid":"0000-0001-7519-1145","position":6,"is_corresponding":false},{"id":1078240,"name":"Francisco Castañeda","orcid":null,"position":7,"is_corresponding":false},{"id":262126,"name":"Ryan E. Yoast","orcid":"0000-0002-7059-6829","position":8,"is_corresponding":false},{"id":262127,"name":"Scott M. Emrich","orcid":"0000-0002-4804-7436","position":9,"is_corresponding":false},{"id":893838,"name":"Priscilla W. Tang","orcid":"0000-0002-6081-4001","position":10,"is_corresponding":false},{"id":147718,"name":"David I Yule","orcid":"0000-0002-6743-0668","position":11,"is_corresponding":false},{"id":240809,"name":"Nadine Hempel","orcid":"0000-0002-5574-8783","position":12,"is_corresponding":false},{"id":1077693,"name":"Marie Potier‐Cartereau","orcid":"0000-0002-1361-3397","position":13,"is_corresponding":false},{"id":262130,"name":"James Sneyd","orcid":"0000-0001-7305-2862","position":14,"is_corresponding":false},{"id":262132,"name":"Mohamed Trebak","orcid":"0000-0001-6759-864X","position":15,"is_corresponding":false},{"id":656427,"name":"J. Cory Benson","orcid":"0000-0002-1446-9972","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T01:11:08.077724Z","pmid":"37778728","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}