{"doi":"10.1016/j.jbc.2023.105418","title":"Kinome profiling identifies MARK3 and STK10 as potential therapeutic targets in uveal melanoma","abstract":"Most uveal melanoma cases harbor activating mutations in either GNAQ or GNA11. Despite activation of the mitogen-activated protein kinase (MAPK) signaling pathway downstream of Gαq/11, there are no effective targeted kinase therapies for metastatic uveal melanoma. The human genome encodes numerous understudied kinases, also called the \"dark kinome\". Identifying additional kinases regulated by Gαq/11 may uncover novel therapeutic targets for uveal melanoma. In this study, we treated GNAQ-mutant uveal melanoma cell lines with a Gαq/11 inhibitor, YM-254890, and conducted a kinase signaling proteomic screen using multiplexed-kinase inhibitors followed by mass spectrometry. We observed downregulated expression and/or activity of 22 kinases. A custom siRNA screen targeting these kinases demonstrated that knockdown of microtubule affinity regulating kinase 3 (MARK3) and serine/threonine kinase 10 (STK10) significantly reduced uveal melanoma cell growth and decreased expression of cell cycle proteins. Additionally, knockdown of MARK3 but not STK10 decreased ERK1/2 phosphorylation. Analysis of RNA-sequencing and proteomic data showed that Gαq signaling regulates STK10 expression and MARK3 activity. Our findings suggest an involvement of STK10 and MARK3 in the Gαq/11 oncogenic pathway and prompt further investigation into the specific roles and targeting potential of these kinases in uveal melanoma.","journal":"Journal of Biological Chemistry","year":2023,"id":354377,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9434,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":485100,"name":"Alison Kurimchak","orcid":"0000-0003-2608-0128","position":1,"is_corresponding":false},{"id":1084557,"name":"Isabella V. Trachtenberg","orcid":"0009-0003-0341-2828","position":2,"is_corresponding":false},{"id":292754,"name":"Timothy J. Purwin","orcid":"0000-0002-7053-8039","position":3,"is_corresponding":false},{"id":1084558,"name":"Jelan I. Haj","orcid":"0009-0001-3576-8955","position":4,"is_corresponding":false},{"id":355994,"name":"Anna Han","orcid":"0000-0001-8180-6214","position":5,"is_corresponding":false},{"id":1101520,"name":"K.X. Luo","orcid":"0000-0002-2894-202X","position":6,"is_corresponding":false},{"id":1001965,"name":"Nikole Fandiño Pachon","orcid":null,"position":7,"is_corresponding":false},{"id":1101960,"name":"Angela Jeon","orcid":null,"position":8,"is_corresponding":false},{"id":355996,"name":"Vivian Chua","orcid":"0000-0002-1873-6820","position":9,"is_corresponding":false},{"id":72141,"name":"Michael A. Davies","orcid":"0000-0002-0977-0912","position":10,"is_corresponding":false},{"id":273870,"name":"J. Silvio Gutkind","orcid":"0000-0002-5150-4482","position":11,"is_corresponding":false},{"id":315488,"name":"Jeffrey Benovic","orcid":"0000-0001-5705-7129","position":12,"is_corresponding":false},{"id":407669,"name":"James S. Duncan","orcid":"0000-0002-1276-2745","position":13,"is_corresponding":false},{"id":336530,"name":"Andrew E. Aplin","orcid":"0000-0002-2734-3244","position":14,"is_corresponding":false},{"id":483227,"name":"Usman Baqai","orcid":"0000-0001-8198-3966","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T01:13:06.959762Z","pmid":"37923138","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":[]}