{"doi":"10.1159/000443126","title":"Decrease of Store-Operated Ca2+ Entry and Increase of Na+/Ca2+ Exchange by Pharmacological JAK2 Inhibition","abstract":"<jats:p>Background/Aims: Cell proliferation and migration are regulated by cytosolic Ca2+ activity ([Ca2+]i). Mechanisms modifying [Ca2+]i include store-operated Ca2+-entry (SOCE) accomplished by the pore-forming ion channel unit Orai1 and its regulator STIM1, as well as Ca2+ extrusion by Na+/Ca2+ exchanger NCX1. Kinases participating in the orchestration of cell proliferation include the Janus activated kinase JAK2. The present study explored the impact of pharmacological JAK2 inhibition on SOCE and Na+/Ca2+ exchange. Methods: MCF-7 breast carcinoma cells were studied in the absence and presence of the JAK2 inhibitors TG101348 (250 nM - 1 µM) or of AG490 (20 - 40 µM). Transcript levels were quantified with RT-PCR, protein abundance with immunoblotting, [Ca2+]i with Fura-2-fluorescence, SOCE from increase of [Ca2+]i following Ca2+ re-addition after Ca2+-store depletion with sarcoendoplasmatic Ca2+-ATPase (SERCA) inhibitor thapsigargin (1 µM), and Na+/Ca2+ exchanger activity from increase of [Ca2+]i as well as Ca2+ current in whole cell patch clamp following extracellular Na+ removal. Migratory activity was determined by a wound healing assay. Results: JAK2 inhibitor TG101348 (1 µM) decreased Orai1 and STIM1 protein abundance, increased NCX1 transcript levels, decreased Ca2+ release from intracellular stores, decreased SOCE, increased Ca2+ entry as well as Ca2+-current following extracellular Na+-removal, and decreased migration. Similar effects on Ca2+ release, SOCE, and Ca2+-entry following extracellular Na+-removal were observed following treatment with AG490. Conclusion: The present observations disclose a novel powerful mechanism regulating intracellular Ca2+ release, cellular Ca2+ entry, cellular Ca2+ extrusion and cell migration.</jats:p>","journal":"Cellular Physiology and Biochemistry","year":2016,"id":29160,"datarank":0.6135578286662833,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.2176992292239944,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.2176992292239944,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":6,"citers_with_citation_signal":6,"citers_with_endowment":6,"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":161447,"name":"Zohreh Hosseinzadeh","orcid":null,"position":1,"is_corresponding":false},{"id":161448,"name":"Bingbing Zhang","orcid":null,"position":2,"is_corresponding":false},{"id":161449,"name":"Mirjam Froeschl","orcid":null,"position":3,"is_corresponding":false},{"id":161450,"name":"Klaus Schulze-Osthoff","orcid":null,"position":4,"is_corresponding":false},{"id":161451,"name":"Christos Stournaras","orcid":null,"position":5,"is_corresponding":false},{"id":80155,"name":"Florian Lang","orcid":null,"position":6,"is_corresponding":false},{"id":161446,"name":"Jing Yan","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.639057329615259,"endowment":2.639057329615259,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26859825","pmcid":null,"openalex_id":"https://openalex.org/W2297014355","authors":[],"funders":[],"total_grants":0,"fwci":1.7855,"citation_percentile":0.8133829,"influential_citations":1,"citation_trend":[{"year":2016,"count":4},{"year":2017,"count":3},{"year":2018,"count":2},{"year":2021,"count":1},{"year":2023,"count":1},{"year":2024,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.karger.com/Article/Pdf/443126","host_type":"journal"},{"url":"https://www.karger.com/Article/Pdf/443126","host_type":"GOLD"},{"url":"https://www.karger.com/Article/Pdf/443126","host_type":"publisher"},{"url":"https://doi.org/10.1159/000443126","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26859825","host_type":"repository"},{"url":"https://doaj.org/article/caee1b0349cd4a29807b3d4799e84943","host_type":"repository"}],"fields_of_study":["Ion Channels and Receptors","Magnesium in Health and Disease","Ion channel regulation and function","Chemistry","Medicine","Calcium","Calcium Channels","Cell Movement","Humans","Janus Kinase 2","MCF-7 Cells","Membrane Proteins","Neoplasm Proteins","ORAI1 Protein","Protein Kinase Inhibitors","Pyridines","Pyrrolidines","Sodium","Sodium-Calcium Exchanger","Stromal Interaction Molecule 1","Sulfonamides","Thiazines","Tyrphostins","Benzenesulfonamides"],"mesh_terms":["Stromal Interaction Molecule 1","ORAI1 Protein","Benzenesulfonamides","Calcium","Cell Movement","Humans","Membrane Proteins","Neoplasm Proteins","Pyridines","Pyrrolidines","Sodium","Sulfonamides","Thiazines","Calcium Channels","Sodium-Calcium Exchanger","Tyrphostins","Protein Kinase Inhibitors","Janus Kinase 2","MCF-7 Cells"],"keywords":["ORAI1","Thapsigargin","Extracellular","Intracellular","Chemistry","STIM1","Cytosol","Cell biology","Sodium-calcium exchanger","SERCA","Plasma membrane Ca2+ ATPase","ATPase","Biochemistry","Biology","Endoplasmic reticulum","Enzyme"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-08T22:46:40.317595Z","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":[]}