{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T21:48:13Z","timestamp":1780436893800,"version":"3.54.1"},"reference-count":36,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,1,16]]},"abstract":"<jats:p>Aggregation of the high affinity IgE receptor (Fc\u025bRI) activates a cascade of signaling events leading to mast cell activation. Subsequently, inhibitory signals are engaged for turning off activating signals. We identified that regulator of calcineurin (Rcan) 1 serves as a negative regulator for turning off Fc\u025bRI-mediated mast cell activation. Fc\u025bRI-induced Rcan1 expression was identified by suppression subtractive hybridization and verified by real-time quantitative polymerase chain reaction and Western blotting. Deficiency of Rcan1 led to increased calcineurin activity, increased nuclear factor of activated T cells and nuclear factor \u03baB activation, increased cytokine production, and enhanced immunoglobulin E\u2013mediated late-phase cutaneous reactions. Forced expression of Rcan1 in wild-type or Rcan1-deficient mast cells reduced Fc\u025bRI-mediated cytokine production. Rcan1 deficiency also led to increased Fc\u025bRI-mediated mast cell degranulation and enhanced passive cutaneous anaphylaxis. Analysis of the Rcan1 promoter identified a functional Egr1 binding site. Biochemical and genetic evidence suggested that Egr1 controls Rcan1 expression. Our results identified Rcan1 as a novel inhibitory signal in Fc\u025bRI-induced mast cell activation and established a new link of Egr1 and Rcan1 in Fc\u025bRI signaling.<\/jats:p>","DOI":"10.1084\/jem.20081140","type":"journal-article","created":{"date-parts":[[2009,1,5]],"date-time":"2009-01-05T20:44:54Z","timestamp":1231188294000},"page":"195-207","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":34,"title":["Rcan1 negatively regulates Fc\u025bRI-mediated signaling and mast cell function"],"prefix":"10.1084","volume":"206","author":[{"given":"Yong Jun","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology and Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Edgar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology, Capital Medical University, Beijing 100069, China 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery D.","family":"Molkentin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason N.","family":"Berman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong-Jun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2009,1,5]]},"reference":[{"key":"2023072916435227700_bib1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nri914","article-title":"Regulation of mast-cell and basophil function and survival by IgE","volume":"2","author":"Kawakami","year":"2002","journal-title":"Nat. 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