{"doi":"10.1242/jcs.260313","title":"WNK1 is a chloride-stimulated scaffold that regulates mTORC2 activity and ion transport","abstract":"Mammalian (or mechanistic) target of rapamycin complex 2 (mTORC2) is a kinase complex that targets predominantly Akt family proteins, SGK1 and protein kinase C (PKC), and has well-characterized roles in mediating hormone and growth factor effects on a wide array of cellular processes. Recent evidence suggests that mTORC2 is also directly stimulated in renal tubule cells by increased extracellular K+ concentration, leading to activation of the Na+ channel, ENaC, and increasing the electrical driving force for K+ secretion. We identify here a signaling mechanism for this local effect of K+. We show that an increase in extracellular [K+] leads to a rise in intracellular chloride (Cl-), which stimulates a previously unknown scaffolding activity of the protein 'with no lysine-1' (WNK1) kinase. WNK1 interacts selectively with SGK1 and recruits it to mTORC2, resulting in enhanced SGK1 phosphorylation and SGK1-dependent activation of ENaC. This scaffolding effect of WNK1 is independent of its own kinase activity and does not cause a generalized stimulation of mTORC2 kinase activity. These findings establish a novel WNK1-dependent regulatory mechanism that harnesses mTORC2 kinase activity selectively toward SGK1 to control epithelial ion transport and electrolyte homeostasis.","journal":"Journal of Cell Science","year":2022,"id":249102,"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":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":889193,"name":"Deise Carla Almeida Leite Dellova","orcid":"0000-0002-3868-1417","position":1,"is_corresponding":false},{"id":889194,"name":"John E. Demko","orcid":"0000-0002-7611-1781","position":2,"is_corresponding":false},{"id":889195,"name":"Mads Vaarby Sørensen","orcid":"0000-0001-6398-1035","position":3,"is_corresponding":false},{"id":884416,"name":"Enzo Takagi","orcid":"0000-0002-2625-686X","position":4,"is_corresponding":false},{"id":729338,"name":"Catherine E. Gleason","orcid":null,"position":5,"is_corresponding":false},{"id":889826,"name":"Waheed Shabbir","orcid":null,"position":6,"is_corresponding":false},{"id":728751,"name":"David Pearce","orcid":"0000-0003-0496-3173","position":7,"is_corresponding":false},{"id":728749,"name":"Bidisha Saha","orcid":"0000-0002-4153-5007","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T00:24:19.356023Z","pmid":"36373794","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":[]}