{"doi":"10.1146/annurev.immunol.021908.132550","title":"Molecular Basis of Calcium Signaling in Lymphocytes: STIM and ORAI","abstract":"<jats:p>Ca<jats:sup>2+</jats:sup>entry into cells of the peripheral immune system occurs through highly Ca<jats:sup>2+</jats:sup>-selective channels known as CRAC (calcium release-activated calcium) channels. CRAC channels are a very well-characterized example of store-operated Ca<jats:sup>2+</jats:sup>channels, so designated because they open when the endoplasmic reticulum (ER) Ca<jats:sup>2+</jats:sup>store becomes depleted. Physiologically, Ca<jats:sup>2+</jats:sup>is released from the ER lumen into the cytoplasm when activated receptors couple to phospholipase C and trigger production of the second messenger inositol 1,4,5-trisphosphate (IP<jats:sub>3</jats:sub>). IP<jats:sub>3</jats:sub>binds to IP<jats:sub>3</jats:sub>receptors in the ER membrane and activates Ca<jats:sup>2+</jats:sup>release. The proteins STIM and ORAI were discovered through limited and genome-wide RNAi screens, respectively, performed in Drosophila cells and focused on identifying modulators of store-operated Ca<jats:sup>2+</jats:sup>entry. STIM1 and STIM2 sense the depletion of ER Ca<jats:sup>2+</jats:sup>stores, whereas ORAI1 is a pore subunit of the CRAC channel. In this review, we discuss selected aspects of Ca<jats:sup>2+</jats:sup>signaling in cells of the immune system, focusing on the roles of STIM and ORAI proteins in store-operated Ca<jats:sup>2+</jats:sup>entry.</jats:p>","journal":"Annual Review of Immunology","year":2010,"id":681531,"datarank":0.9955887046926687,"base_score":6.637258031284457,"endowment":6.637258031284457,"self_citation_contribution":0.9955887046926687,"citation_network_contribution":0.0,"self_endowment_contribution":0.9955887046926687,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":762,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":568735,"name":"Richard S. 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Physiologically, Ca<jats:sup>2+</jats:sup>is released from the ER lumen into the cytoplasm when activated receptors couple to phospholipase C and trigger production of the second messenger inositol 1,4,5-trisphosphate (IP<jats:sub>3</jats:sub>). IP<jats:sub>3</jats:sub>binds to IP<jats:sub>3</jats:sub>receptors in the ER membrane and activates Ca<jats:sup>2+</jats:sup>release. The proteins STIM and ORAI were discovered through limited and genome-wide RNAi screens, respectively, performed in Drosophila cells and focused on identifying modulators of store-operated Ca<jats:sup>2+</jats:sup>entry. STIM1 and STIM2 sense the depletion of ER Ca<jats:sup>2+</jats:sup>stores, whereas ORAI1 is a pore subunit of the CRAC channel. In this review, we discuss selected aspects of Ca<jats:sup>2+</jats:sup>signaling in cells of the immune system, focusing on the roles of STIM and ORAI proteins in store-operated Ca<jats:sup>2+</jats:sup>entry.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26207759","pmcid":null,"openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2861828","host_type":"repository"},{"url":"https://www.annualreviews.org/doi/pdf/10.1146/annurev.immunol.021908.132550","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":[],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T18:01:42.614732Z","pmid":null,"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":[]}