{"doi":"10.1074/jbc.ra120.014464","title":"PRL3 pseudophosphatase activity is necessary and sufficient to promote metastatic growth","abstract":"Phosphatases of regenerating liver (PRLs) are markers of cancer and promote tumor growth. They have been implicated in a variety of biochemical pathways but the physiologically relevant target of phosphatase activity has eluded 20 years of investigation. Here, we show that PRL3 catalytic activity is not required in a mouse model of metastasis. PRL3 binds and inhibits CNNM4, a membrane protein associated with magnesium transport. Analysis of PRL3 mutants specifically defective in either CNNM-binding or phosphatase activity demonstrate that CNNM binding is necessary and sufficient to promote tumor metastasis. As PRLs do have phosphatase activity, they are in fact pseudo-pseudophosphatases. Phosphatase activity leads to formation of phosphocysteine, which blocks CNNM binding and may play a regulatory role. We show levels of PRL cysteine phosphorylation vary in response to culture conditions and in different tissues. Examination of related protein phosphatases shows the stability of phosphocysteine is a unique and evolutionarily conserved property of PRLs. The demonstration that PRL3 functions as a pseudophosphatase has important ramifications for the design of PRL inhibitors for cancer.","journal":"Journal of Biological Chemistry","year":2020,"id":95374,"datarank":1.1053443818306896,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.5637066949340559,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.5637066949340559,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":20,"citers_with_citation_signal":17,"citers_with_endowment":17,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":true,"deposit_databanks":{"PDB":["5K22","5K23","5TSR"]},"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":245019,"name":"Yosuke Funato","orcid":"0000-0002-4288-7717","position":1,"is_corresponding":false},{"id":473782,"name":"Yu Seby Chen","orcid":"0000-0002-0793-2391","position":2,"is_corresponding":false},{"id":473783,"name":"Zhidian Zhang","orcid":"0000-0002-5658-7395","position":3,"is_corresponding":false},{"id":474424,"name":"Katalin Illes","orcid":null,"position":4,"is_corresponding":false},{"id":245020,"name":"Hiroaki Miki","orcid":"0000-0003-0454-7006","position":5,"is_corresponding":false},{"id":473784,"name":"Kalle Gehring","orcid":"0000-0001-6500-1184","position":6,"is_corresponding":false},{"id":473781,"name":"Guennadi Kozlov","orcid":"0000-0002-7742-6558","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-18T22:33:30.364261Z","pmid":"32571875","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":[]}