{"doi":"10.17615/m456-ck78","title":"Counteracting Signaling Activities in Lipid Rafts Associated with the Invasion of Lung Epithelial Cells by Pseudomonas aeruginosa","abstract":"Pseudomonas aeruginosa has the capacity to invade lung epithelial cells by co-opting the intrinsic endocytic properties of lipid rafts, which are rich in cholesterol, sphingolipids, and proteins, such as caveolin-1 and -2. We compared intratracheal Pseudomonas infection in wild type and caveolin-deficient mice to investigate the role of caveolin proteins in the pathogenesis of Pseudomonas pneumonia. Unlike wild type mice, which succumb to pneumonia, caveolin-deficient mice are resistant to Pseudomonas. We observed that Pseudomonas invasion of lung epithelial cells is dependent on caveolin-2 but not caveolin-1. Phosphorylation of caveolin-2 by Src family kinases is an essential event for Pseudomonas invasion. Our studies also reveal the existence of a distinct signaling mechanism in lung epithelial cells mediated by COOH-terminal Src kinase (Csk) that negatively regulates Pseudomonas invasion. Csk migrates to lipid raft domains, where it decreases phosphorylation of caveolin-2 by inactivating c-Src. Whereas Pseudomonas co-opts the endocytic properties of caveolin-2 for invasion, there also exists in these cells an intrinsic Csk-dependent cellular defense mechanism aimed at impairing this activity. The success of Pseudomonas in co-opting lipid raft-mediated endocytosis to invade lung epithelial cells may depend on the relative strengths of these counteracting signaling activities.","journal":"UNC Libraries","year":2020,"id":138956,"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":0.9473,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":601683,"name":"Zachary D. Swan","orcid":null,"position":1,"is_corresponding":false},{"id":601025,"name":"Mary E. Sunday","orcid":"0000-0002-6788-1469","position":2,"is_corresponding":false},{"id":601026,"name":"Guojie Li","orcid":"0000-0002-0524-961X","position":3,"is_corresponding":false},{"id":72632,"name":"Scott H. Randell","orcid":"0000-0001-5351-2841","position":4,"is_corresponding":false},{"id":601684,"name":"David Zaas","orcid":null,"position":5,"is_corresponding":false},{"id":336274,"name":"Simone Degan","orcid":"0000-0001-5417-1196","position":6,"is_corresponding":false},{"id":53023,"name":"Soman N. Abraham","orcid":"0000-0002-1662-2096","position":7,"is_corresponding":false},{"id":601685,"name":"Bethany J. Brown","orcid":null,"position":8,"is_corresponding":false},{"id":548977,"name":"Jo Rae Wright","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:06.651725Z","pmid":null,"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":[]}