{"doi":"10.1002/eji.201948442","title":"Negative control of diacylglycerol kinase ζ‐mediated inhibition of T cell receptor signaling by nuclear sequestration in mice","abstract":"Diacylglycerol kinases (DGKs) play important roles in restraining diacylglycerol (DAG)-mediated signaling. Within the DGK family, the ζ isoform appears to be the most important isoform in T cells for controlling their development and function. DGKζ has been demonstrated to regulate T cell maturation, activation, anergy, effector/memory differentiation, defense against microbial infection, and antitumor immunity. Given its critical functions, DGKζ function should be tightly regulated to ensure proper signal transduction; however, mechanisms that control DGKζ function are still poorly understood. We report here that DGKζ dynamically translocates from the cytosol into the nuclei in T cells after TCR stimulation. In mice, DGKζ mutant defective in nuclear localization displayed enhanced ability to inhibit TCR-induced DAG-mediated signaling in primary T cells, maturation of conventional αβT and iNKT cells, and activation of peripheral T cells compared with WT DGKζ. Our study reveals for the first time nuclear sequestration of DGKζ as a negative control mechanism to spatially restrain it from terminating DAG mediated signaling in T cells. Our data suggest that manipulation of DGKζ nucleus-cytosol shuttling as a novel strategy to modulate DGKζ activity and immune responses for treatment of autoimmune diseases and cancer.","journal":"European Journal of Immunology","year":2020,"id":108975,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":521655,"name":"Shimeng Zhang","orcid":null,"position":1,"is_corresponding":false},{"id":520950,"name":"Pengcheng Chen","orcid":"0000-0002-7989-0194","position":2,"is_corresponding":false},{"id":520951,"name":"Wenhai Deng","orcid":"0000-0003-3270-5980","position":3,"is_corresponding":false},{"id":520952,"name":"Yun Pan","orcid":"0000-0002-3832-3433","position":4,"is_corresponding":false},{"id":380107,"name":"Jinhai Xie","orcid":null,"position":5,"is_corresponding":false},{"id":379414,"name":"Jinli Wang","orcid":"0000-0003-3453-3692","position":6,"is_corresponding":false},{"id":521656,"name":"Bryce Liao","orcid":null,"position":7,"is_corresponding":false},{"id":381040,"name":"John W. Sleasman","orcid":"0000-0003-0078-5867","position":8,"is_corresponding":false},{"id":379416,"name":"Xiao‐Ping Zhong","orcid":"0000-0002-4619-8783","position":9,"is_corresponding":false},{"id":521654,"name":"Danli Xie","orcid":null,"position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-18T23:12:46.854423Z","pmid":"32525220","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":[]}