{"doi":"10.1126/scisignal.ade1119","title":"Chemokine-mediated F-actin dynamics, polarity, and migration in B lymphocytes depend on WNK1 signaling","abstract":"Ligand-engaged chemokine receptors trigger nucleotide exchange in heterotrimeric Gα i proteins, which stimulates cytoskeletal reorganization and cell polarity changes. To better understand the signaling events responsible for these cellular changes, we focused on early changes in F-actin dynamics after engagement of the chemokine receptor CXCR5 in murine splenic B cells. Within 10 seconds of exposure to the CXCR5 ligand CXCL13, three-dimensional lamellar-like pseudopods and F-actin–rich ridges appeared. The transient F-actin increase depended on Gα i2/3 signaling, the PI3K/AKT pathway, ERK activation, phospholipase C activity, and Rac1/2 activation mediated by Dock2 (dedicator of cytokinesis 2). Immunoblot analyses identified the kinase WNK1 (with no lysine kinase 1) as a potential early AKT effector. Treating B cells with specific WNK inhibitors disrupted F-actin dynamics and impaired B cell polarity, motility, and chemotaxis. These changes were mimicked in a murine B cell line by CRISPR-Cas9 gene editing of Wnk1 , which also suggested that WNK1 contributed to B cell proliferation. Administration of a single dose of a WNK inhibitor transiently reduced B cell motility and polarity in the lymph nodes of live mice. These results indicate that WNK1 signaling maintains B cell responsiveness to CXCL13 and suggest that pharmacological inhibition of WNK1, which is involved in cancer progression and blood pressure regulation, may affect humoral immunity.","journal":"Science Signaling","year":2024,"id":449134,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1268945,"name":"Ji Sung Kim","orcid":null,"position":1,"is_corresponding":false},{"id":297560,"name":"Kathleen A. Harrison","orcid":"0000-0003-0080-567X","position":2,"is_corresponding":false},{"id":1268483,"name":"Chung Park","orcid":"0000-0002-7819-5333","position":3,"is_corresponding":false},{"id":1268946,"name":"Chong Shi","orcid":null,"position":4,"is_corresponding":false},{"id":109652,"name":"John H. Kehrl","orcid":"0000-0002-6526-159X","position":5,"is_corresponding":false},{"id":297561,"name":"Il‐Young Hwang","orcid":"0000-0003-4498-4382","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T02:02:16.291892Z","pmid":"39190707","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":[]}