{"doi":"10.3390/cells11243972","title":"c-Abl Regulates the Pathological Deposition of TDP-43 via Tyrosine 43 Phosphorylation","abstract":"Non-receptor tyrosine kinase, c-Abl plays a role in the pathogenesis of several neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Here, we found that TDP-43, which was one of the main proteins comprising pathological deposits in amyotrophic lateral sclerosis (ALS), is a novel substrate for c-Abl. The phosphorylation of tyrosine 43 of TDP-43 by c-Abl led to increased TDP-43 levels in the cytoplasm and increased the formation of G3BP1-positive stress granules in SH-SY5Y cells. The kinase-dead mutant of c-Abl had no effect on the cytoplasmic localization of TDP-43. The expression of phosphor-mimetic mutant Y43E of TDP-43 in primary cortical neurons accumulated the neurite granule. Furthermore, the phosphorylation of TDP-43 at tyrosine 43 by c-Abl promoted the aggregation of TDP-43 and increased neuronal cell death in primary cortical neurons, but not in c-Abl-deficient primary cortical neurons. Identification of c-Abl as the kinase of TDP43 provides new insight into the pathogenesis of ALS.","journal":"Cells","year":2022,"id":264750,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9576,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":922859,"name":"Hye Guk Ryu","orcid":"0000-0002-5901-1316","position":1,"is_corresponding":false},{"id":922860,"name":"Sin Ho Kweon","orcid":"0000-0002-9363-6010","position":2,"is_corresponding":false},{"id":923316,"name":"Hyerynn Kim","orcid":null,"position":3,"is_corresponding":false},{"id":922861,"name":"Hyeonwoo Park","orcid":"0000-0003-2562-4656","position":4,"is_corresponding":false},{"id":922862,"name":"Kyung‐Ha Lee","orcid":"0000-0003-0515-7392","position":5,"is_corresponding":false},{"id":293633,"name":"Sang‐Min Jang","orcid":null,"position":6,"is_corresponding":false},{"id":305261,"name":"Chan Hyun Na","orcid":"0000-0002-3622-2938","position":7,"is_corresponding":false},{"id":922863,"name":"Sangjune Kim","orcid":"0000-0003-3052-3163","position":8,"is_corresponding":false},{"id":604404,"name":"Han Seok Ko","orcid":null,"position":9,"is_corresponding":false},{"id":624195,"name":"Saebom Lee","orcid":"0000-0001-9450-1620","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T00:26:41.845195Z","pmid":"36552734","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":[]}