{"doi":"10.1091/mbc.11.8.2793","title":"Differential Modulation of Cadherin-mediated Cell–Cell Adhesion by Platelet Endothelial Cell Adhesion Molecule-1 Isoforms through Activation of Extracellular Regulated Kinases","abstract":"<jats:p>The role of platelet endothelial cell adhesion molecule-1 (PECAM-1) in endothelial cell–cell interactions and its contribution to cadherin-mediated cell adhesion are poorly understood. Such studies have been difficult because all known endothelial cells express PECAM-1. We have used Madin-Darby canine kidney (MDCK) cells as a model system in which to evaluate the role of PECAM-1 isoforms that differ in their cytoplasmic domains in cell–cell interactions. MDCK cells lack endogenous PECAM-1 but form cell–cell junctions similar to those of endothelial cells, in which PECAM-1 is concentrated. MDCK cells were transfected with two isoforms of murine PECAM-1, Δ15 and Δ14&amp;15, the predominant isoforms expressed in vivo. Expression of the Δ15 isoform resulted in apparent dedifferentiation of MDCK cells concomitant with the loss of adherens junctions, down-regulation of E-cadherin, α- and β-catenin expression, and sustained activation of extracellular regulated kinases. The Δ15 isoform was not concentrated at cell–cell contacts. In contrast, the Δ14&amp;15 isoform localized to sites of cell–cell contact and had no effect on MDCK cell morphology, cadherin/catenin expression, or extracellular regulated kinase activity. Thus, the presence of exon 14 in the cytoplasmic domain of PECAM-1 has dramatic effects on the ability of cells to maintain adherens junctions and an epithelial phenotype. Therefore, changes in the expression of exon 14 containing PECAM-1 isoforms, which we have observed during development, may have profound functional consequences.</jats:p>","journal":"Molecular Biology of the Cell","year":2000,"id":590136,"datarank":1.5097229131663572,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"self_citation_contribution":0.5495342469194471,"citation_network_contribution":0.9601886662469102,"self_endowment_contribution":0.5495342469194471,"citer_contribution":0.9601886662469102,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":24,"citers_with_citation_signal":20,"citers_with_endowment":20,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":405229,"name":"Christine M. Sorenson","orcid":"0000-0001-8461-6619","position":1,"is_corresponding":false},{"id":1352339,"name":"William A. Frazier","orcid":null,"position":2,"is_corresponding":false},{"id":382555,"name":"Nader Sheibani","orcid":"0000-0003-2723-9217","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Differential Modulation of Cadherin-mediated Cell–Cell Adhesion by Platelet Endothelial Cell Adhesion Molecule-1 Isoforms through Activation of Extracellular Regulated Kinases","abstract":"<jats:p>The role of platelet endothelial cell adhesion molecule-1 (PECAM-1) in endothelial cell–cell interactions and its contribution to cadherin-mediated cell adhesion are poorly understood. Such studies have been difficult because all known endothelial cells express PECAM-1. We have used Madin-Darby canine kidney (MDCK) cells as a model system in which to evaluate the role of PECAM-1 isoforms that differ in their cytoplasmic domains in cell–cell interactions. MDCK cells lack endogenous PECAM-1 but form cell–cell junctions similar to those of endothelial cells, in which PECAM-1 is concentrated. MDCK cells were transfected with two isoforms of murine PECAM-1, Δ15 and Δ14&amp;15, the predominant isoforms expressed in vivo. Expression of the Δ15 isoform resulted in apparent dedifferentiation of MDCK cells concomitant with the loss of adherens junctions, down-regulation of E-cadherin, α- and β-catenin expression, and sustained activation of extracellular regulated kinases. The Δ15 isoform was not concentrated at cell–cell contacts. In contrast, the Δ14&amp;15 isoform localized to sites of cell–cell contact and had no effect on MDCK cell morphology, cadherin/catenin expression, or extracellular regulated kinase activity. Thus, the presence of exon 14 in the cytoplasmic domain of PECAM-1 has dramatic effects on the ability of cells to maintain adherens junctions and an epithelial phenotype. Therefore, changes in the expression of exon 14 containing PECAM-1 isoforms, which we have observed during development, may have profound functional consequences.</jats:p>","is_dataset_classified":null,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10930470","pmcid":"PMC14956","openalex_id":"https://openalex.org/W2120995033","authors":[],"funders":[{"funder_name":"NIAMS NIH HHS","grant_id":"AR 45599","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA 65872","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"R01 AR045599","title":null}],"total_grants":3,"fwci":2.1271,"citation_percentile":0.87259543,"influential_citations":0,"citation_trend":[{"year":2013,"count":2},{"year":2014,"count":1},{"year":2015,"count":1},{"year":2016,"count":3},{"year":2024,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://doi.org/10.1091/mbc.11.8.2793","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10930470","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/14956","host_type":"repository"}],"fields_of_study":["Platelet Disorders and Treatments","Cell Adhesion Molecules Research","Erythrocyte Function and Pathophysiology","Animals","Cadherins","Cell Adhesion","Cell Line","Cytoskeletal Proteins","Dogs","Enzyme Inhibitors","Epithelial Cells","Flavonoids","Intercellular Junctions","Mitogen-Activated Protein Kinases","Mutagenesis, Site-Directed","Platelet Endothelial Cell Adhesion Molecule-1","Protein Isoforms","Signal Transduction","Trans-Activators","Transfection","beta Catenin"],"mesh_terms":["Animals","Cell Adhesion","Cell Line","Cytoskeletal Proteins","Dogs","Enzyme Inhibitors","Epithelial Cells","Flavonoids","Intercellular Junctions","Transfection","Signal Transduction","Trans-Activators","Cadherins","Mutagenesis, Site-Directed","Platelet Endothelial Cell Adhesion Molecule-1","Protein Isoforms","Mitogen-Activated Protein Kinases","beta Catenin"],"keywords":["Adherens junction","Cell biology","Biology","Cell adhesion","Cell adhesion molecule","Cell–cell interaction","Cadherin","Endothelial stem cell","Cell junction","Cell","Biochemistry","In vitro"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-24T13:42:26.452932Z","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":[]}