{"doi":"10.1159/000549040","title":"Phospho-Proteomic Analysis of Interleukin-13 Signaling in Airway Cells Reveals SRC Family Kinase Involvement in Interleukin-13-Induced Inflammatory Responses","abstract":"INTRODUCTION: Allergic asthma is a chronic inflammatory airway disease driven by the cytokine interleukin-13 (IL-13). Although IL-13 signals through the canonical JAK1/TYK2/STAT6 pathway, our understanding of the totality of IL-13-induced signaling intermediates is incomplete. METHODS: To address this, we performed a phospho-proteomic analysis of IL-13-stimulated A549 human airway epithelial cells. IL-13 stimulation led to differential phosphorylation at 145 unique serine/threonine residues across 92 proteins involved in diverse cellular processes. In silico analysis was used to predict kinases responsible for the observed changes, and therapeutics which may reduce IL-13-mediated pathology. The activation of these kinases and the ability of these therapeutics to limit IL-13 activity were tested in vitro using molecular techniques and in vivo in an IL-13-induced model of asthma. RESULTS: Analysis of IL-13-induced differentially phosphorylated proteins revealed activation of several pathways including RNA splicing, cytoskeletal remodeling, GTPase activity, and focal adhesion complex formation. Network analysis identified SRC family kinases (SFKs), a family of non-receptor tyrosine kinases, as potential regulators of IL-13-induced changes in phosphorylation, and dasatinib, a pan-SFK inhibitor, as a potential inhibitor of IL-13 signaling. In both human and mouse lung fibroblasts, molecular approaches demonstrated activation of SFKs following IL-13 stimulation. In vitro, dasatinib reduced IL-13-induced STAT6 phosphorylation and downstream gene expression. In vivo, dasatinib attenuated IL-13-induced airway hyperresponsiveness without significantly affecting inflammatory cell infiltration or gene expression in bronchoalveolar lavage fluid. CONCLUSION: These findings support a potential therapeutic role for dasatinib in inhibition of IL-13-driven responses such as those observed in allergic asthma.","journal":"International Archives of Allergy and Immunology","year":2025,"id":580667,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":597349,"name":"Jaclyn W. McAlees","orcid":"0000-0002-2589-5010","position":1,"is_corresponding":false},{"id":455025,"name":"Michael A. Wyder","orcid":"0000-0001-7355-2250","position":2,"is_corresponding":false},{"id":1378980,"name":"Julie Hargis","orcid":null,"position":3,"is_corresponding":false},{"id":1174266,"name":"Harshavardhana H. Ediga","orcid":"0000-0002-2809-5449","position":4,"is_corresponding":false},{"id":1492139,"name":"Angela Cannata","orcid":null,"position":5,"is_corresponding":false},{"id":1383476,"name":"Jana Latayan","orcid":"0009-0001-7520-2737","position":6,"is_corresponding":false},{"id":87808,"name":"Kenneth D. Greis","orcid":"0000-0002-5316-3351","position":7,"is_corresponding":false},{"id":416432,"name":"Satish K. Madala","orcid":"0000-0002-6042-5321","position":8,"is_corresponding":false},{"id":302690,"name":"Ian Lewkowich","orcid":"0000-0001-8133-3568","position":9,"is_corresponding":false},{"id":854353,"name":"Archana Shankar","orcid":"0000-0002-8870-9262","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T02:58:43.046112Z","pmid":"41212792","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":[]}