title: Localization of LAT in glycolipid-enriched microdomains is required for T cell activation.
abstract: LAT, a transmembrane adapter protein found in glycolipid-enriched microdomains (GEMs), is essential for T cell activation. In this study, we have utilized a LAT-deficient mutant of the Jurkat T cell line, J.CaM2, to explore various requirements for LAT function. First, we demonstrate that LAT must be present in GEMs for coupling T cell receptor (TCR) engagement to activation of the Ras signaling pathway, increases in intracellular Ca(2+), and induction of the transcription factor nuclear factor of activated T cells (NF-AT). Second, we show that the extracellular and transmembrane domains of LAT are dispensable for these TCR-mediated events once LAT has localized to GEMs. These results provide important insights into both the structural domains of LAT and its subcellular localization that are required for effective TCR signaling.
authors.affiliation: Department of Medicine, Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94143, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.forename: A
authors.initials: A
authors.lastname: Weiss
authors.forename: T S
authors.initials: TS
authors.lastname: Finco
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006017:Glycolipids / Q000737:chemistry*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics*; D008565:Membrane Proteins / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006017:Glycolipids; C110810:LAT protein, human; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D019000:Phosphotyrosine; D019950:Mitogen-Activated Protein Kinase 1; D018631:ras Proteins; D002118:Calcium