{"doi":"10.1083/jcb.201903031","title":"A polybasic domain in aPKC mediates Par6-dependent control of membrane targeting and kinase activity","abstract":"Mechanisms coupling the atypical PKC (aPKC) kinase activity to its subcellular localization are essential for cell polarization. Unlike other members of the PKC family, aPKC has no well-defined plasma membrane (PM) or calcium binding domains, leading to the assumption that its subcellular localization relies exclusively on protein-protein interactions. Here we show that in both Drosophila and mammalian cells, the pseudosubstrate region (PSr) of aPKC acts as a polybasic domain capable of targeting aPKC to the PM via electrostatic binding to PM PI4P and PI(4,5)P2. However, physical interaction between aPKC and Par-6 is required for the PM-targeting of aPKC, likely by allosterically exposing the PSr to bind PM. Binding of Par-6 also inhibits aPKC kinase activity, and such inhibition can be relieved through Par-6 interaction with apical polarity protein Crumbs. Our data suggest a potential mechanism in which allosteric regulation of polybasic PSr by Par-6 couples the control of both aPKC subcellular localization and spatial activation of its kinase activity.","journal":"The Journal of Cell Biology","year":2020,"id":91799,"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":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"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":459438,"name":"Juan Lu","orcid":"0000-0001-5635-3233","position":1,"is_corresponding":false},{"id":319922,"name":"Xuejing Zhang","orcid":"0000-0003-2994-5502","position":2,"is_corresponding":false},{"id":459439,"name":"Yan Wu","orcid":"0000-0001-6546-9983","position":3,"is_corresponding":false},{"id":459440,"name":"Kaela S. Lettieri","orcid":"0000-0002-9781-1752","position":4,"is_corresponding":false},{"id":245412,"name":"Gerald Hammond","orcid":"0000-0002-6660-3272","position":5,"is_corresponding":false},{"id":459441,"name":"Yang Hong","orcid":"0000-0003-2252-0798","position":6,"is_corresponding":false},{"id":459437,"name":"Wei Dong","orcid":"0000-0001-5519-4859","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T22:29:21.932251Z","pmid":"32580209","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":[]}