title: LIME mediates immunological synapse formation through activation of VAV.
abstract: Lck Interacting Membrane protein (LIME) was previously characterized as a transmembrane adaptor protein mediating TCR-dependent T cell activation. Here, we show that LIME associates with Vav in response to TCR stimulation and is required for Vav guanine nucleotide exchange factor (GEF) activity for Rac1. Consistent with this finding, actin polymerization at the immunological synapse (IS) was markedly enhanced by overexpression of LIME, but was reduced by expression of a LIME shRNA. Moreover, TCR-mediated cell adhesion to ICAM-1, laminin, or fibronectin was downregulated by expression of LIME shRNA. In addition, in the IS, LIME but not LAT was found to localize at the peripheral-supramolecular activation cluster (p-SMAC) where the integrins were previously shown to be localized. Together, these results establish LIME as a transmembrane adaptor protein linking TCR stimulation to IS formation and integrin activation through activation of Vav.
authors.affiliation: Department of Life Science, Ewha Womans' University, Seoul 120-750, Korea.
authors.forename: Myoungsun
authors.initials: M
authors.lastname: Son
authors.forename: Inyoung
authors.initials: I
authors.lastname: Park
authors.forename: Ok-Hee
authors.initials: OH
authors.lastname: Lee
authors.forename: Inmoo
authors.initials: I
authors.lastname: Rhee
authors.forename: Changwon
authors.initials: C
authors.lastname: Park
authors.forename: Yungdae
authors.initials: Y
authors.lastname: Yun
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D011485:Protein Binding; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D015533:Transcriptional Activation; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; C110810:LAT protein, human; C545591:LIME1 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D051567:Proto-Oncogene Proteins c-vav; C107953:RAC1 protein, human; D011948:Receptors, Antigen, T-Cell; D020830:rac1 GTP-Binding Protein