{"doi":"10.15252/embj.2019103695","title":"Mechanisms of site‐specific dephosphorylation and kinase opposition imposed by PP2A regulatory subunits","abstract":"PP2A is an essential protein phosphatase that regulates most cellular processes through the formation of holoenzymes containing distinct regulatory B-subunits. Only a limited number of PP2A-regulated phosphorylation sites are known. This hampers our understanding of the mechanisms of site-specific dephosphorylation and of its tumor suppressor functions. Here, we develop phosphoproteomic strategies for global substrate identification of PP2A-B56 and PP2A-B55 holoenzymes. Strikingly, we find that B-subunits directly affect the dephosphorylation site preference of the PP2A catalytic subunit, resulting in unique patterns of kinase opposition. For PP2A-B56, these patterns are further modulated by affinity and position of B56 binding motifs. Our screens identify phosphorylation sites in the cancer target ADAM17 that are regulated through a conserved B56 binding site. Binding of PP2A-B56 to ADAM17 protease decreases growth factor signaling and tumor development in mice. This work provides a roadmap for the identification of phosphatase substrates and reveals unexpected mechanisms governing PP2A dephosphorylation site specificity and tumor suppressor function.","journal":"The EMBO Journal","year":2020,"id":53704,"datarank":0.7104297672591745,"base_score":4.736198448394496,"endowment":4.736198448394496,"self_citation_contribution":0.7104297672591745,"citation_network_contribution":0.0,"self_endowment_contribution":0.7104297672591745,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":113,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"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":274542,"name":"Sebastian Gnosa","orcid":"0000-0003-2055-2382","position":1,"is_corresponding":false},{"id":273954,"name":"Isha Nasa","orcid":"0000-0001-7699-795X","position":2,"is_corresponding":false},{"id":276408,"name":"Dimitriya H. Garvanska","orcid":null,"position":3,"is_corresponding":false},{"id":274543,"name":"Jamin B. Hein","orcid":"0000-0002-2887-5082","position":4,"is_corresponding":false},{"id":274544,"name":"Hieu Nguyen","orcid":"0000-0003-2153-9200","position":5,"is_corresponding":false},{"id":274545,"name":"Jacob Samsøe‐Petersen","orcid":"0000-0001-9763-2175","position":6,"is_corresponding":false},{"id":274546,"name":"Blanca López‐Méndez","orcid":"0000-0001-8541-4904","position":7,"is_corresponding":false},{"id":274547,"name":"Emil Peter Thrane Hertz","orcid":"0000-0001-6996-3559","position":8,"is_corresponding":false},{"id":276409,"name":"Jeanette Schwarz","orcid":null,"position":9,"is_corresponding":false},{"id":276410,"name":"Hanna Sofia Pena","orcid":null,"position":10,"is_corresponding":false},{"id":274548,"name":"Denise Nikodemus","orcid":"0000-0003-4492-817X","position":11,"is_corresponding":false},{"id":274549,"name":"Marie Kveiborg","orcid":"0000-0002-1293-1019","position":12,"is_corresponding":false},{"id":273955,"name":"Arminja N. Kettenbach","orcid":"0000-0003-3979-4576","position":13,"is_corresponding":false},{"id":274550,"name":"Jakob Nilsson","orcid":"0000-0003-4100-1125","position":14,"is_corresponding":false},{"id":274541,"name":"Thomas Kruse","orcid":"0000-0002-2619-7388","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T20:45:25.145885Z","pmid":"32400009","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":[]}