{"doi":"10.1371/journal.pbio.3001281","title":"The nonreceptor tyrosine kinase SRMS inhibits autophagy and promotes tumor growth by phosphorylating the scaffolding protein FKBP51","abstract":"Nutrient-responsive protein kinases control the balance between anabolic growth and catabolic processes such as autophagy. Aberrant regulation of these kinases is a major cause of human disease. We report here that the vertebrate nonreceptor tyrosine kinase Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (SRMS) inhibits autophagy and promotes growth in a nutrient-responsive manner. Under nutrient-replete conditions, SRMS phosphorylates the PHLPP scaffold FK506-binding protein 51 (FKBP51), disrupts the FKBP51-PHLPP complex, and promotes FKBP51 degradation through the ubiquitin-proteasome pathway. This prevents PHLPP-mediated dephosphorylation of AKT, causing sustained AKT activation that promotes growth and inhibits autophagy. SRMS is amplified and overexpressed in human cancers where it drives unrestrained AKT signaling in a kinase-dependent manner. SRMS kinase inhibition activates autophagy, inhibits cancer growth, and can be accomplished using the FDA-approved tyrosine kinase inhibitor ibrutinib. This illuminates SRMS as a targetable vulnerability in human cancers and as a new target for pharmacological induction of autophagy in vertebrates.","journal":"PLoS Biology","year":2021,"id":191969,"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":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":500990,"name":"Seung Wook Yang","orcid":"0000-0003-4477-0077","position":1,"is_corresponding":false},{"id":581256,"name":"Wei Zhuang","orcid":"0000-0002-1720-8882","position":2,"is_corresponding":false},{"id":453451,"name":"Asim K. Bera","orcid":"0000-0001-9473-2912","position":3,"is_corresponding":false},{"id":758385,"name":"Yan Liu","orcid":"0000-0002-2067-4569","position":4,"is_corresponding":false},{"id":497053,"name":"Deepak Gurbani","orcid":"0000-0002-0982-7173","position":5,"is_corresponding":false},{"id":759038,"name":"Sergei J. von Hoyningen-Huene","orcid":null,"position":6,"is_corresponding":false},{"id":453710,"name":"Sadie Miki Sakurada","orcid":null,"position":7,"is_corresponding":false},{"id":746006,"name":"Haiyun Gan","orcid":"0000-0002-0293-8778","position":8,"is_corresponding":false},{"id":250571,"name":"Shondra M. Pruett‐Miller","orcid":"0000-0002-3793-585X","position":9,"is_corresponding":false},{"id":363328,"name":"Kenneth D. Westover","orcid":"0000-0003-3653-5923","position":10,"is_corresponding":false},{"id":452521,"name":"Malia B. Potts","orcid":"0000-0002-8308-1963","position":11,"is_corresponding":false},{"id":758384,"name":"Jung Mi Park","orcid":"0000-0002-7556-5175","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-18T23:49:39.281850Z","pmid":"34077419","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":[]}