{"doi":"10.1242/jcs.248328","title":"LFA-1 signals to promote actin polymerization and upstream migration in T cells","abstract":"T cell entry into inflamed tissue requires firm adhesion, cell spreading, and migration along and through the endothelial wall. These events require the T cell integrins LFA-1 and VLA-4 and their endothelial ligands ICAM-1 and VCAM-1, respectively. T cells migrate against the direction of shear flow on ICAM-1 and with the direction of shear flow on VCAM-1, suggesting that these two ligands trigger distinct cellular responses. However, the contribution of specific signaling events downstream of LFA-1 and VLA-4 has not been explored. Using primary mouse T cells, we found that engagement of LFA-1, but not VLA-4, induces cell shape changes associated with rapid 2D migration. Moreover, LFA-1 ligation results in activation of the phosphoinositide 3-kinase (PI3K) and ERK pathways, and phosphorylation of multiple kinases and adaptor proteins, whereas VLA-4 ligation triggers only a subset of these signaling events. Importantly, T cells lacking Crk adaptor proteins, key LFA-1 signaling intermediates, or the ubiquitin ligase cCbl (also known as CBL), failed to migrate against the direction of shear flow on ICAM-1. These studies identify novel signaling differences downstream of LFA-1 and VLA-4 that drive T cell migratory behavior.This article has an associated First Person interview with the first author of the paper.","journal":"Journal of Cell Science","year":2020,"id":66902,"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":49,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"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":354225,"name":"Sarah Hyun Ji Kim","orcid":"0000-0002-8116-4466","position":1,"is_corresponding":false},{"id":307278,"name":"Alexander Buffone","orcid":"0000-0003-0303-0152","position":2,"is_corresponding":false},{"id":279476,"name":"Daniel Blumenthal","orcid":"0000-0002-9207-5848","position":3,"is_corresponding":false},{"id":354226,"name":"Bonnie Huang","orcid":"0000-0001-5931-6075","position":4,"is_corresponding":false},{"id":354227,"name":"Sangya Agarwal","orcid":"0000-0003-4272-515X","position":5,"is_corresponding":false},{"id":245103,"name":"Pamela L. Schwartzberg","orcid":"0000-0001-6318-9187","position":6,"is_corresponding":false},{"id":231180,"name":"Daniel A. Hammer","orcid":"0000-0002-3522-3154","position":7,"is_corresponding":false},{"id":279477,"name":"Janis K. Burkhardt","orcid":"0000-0002-8176-1375","position":8,"is_corresponding":false},{"id":313558,"name":"Nathan H. Roy","orcid":"0000-0003-1229-2808","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T21:14:50.590588Z","pmid":"32907931","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":[]}