title: Linker for activation of T cells is displaced from lipid rafts and decreases in lupus T cells after activation via the TCR/CD3 pathway.
abstract: Systemic lupus erythematosus (SLE) is characterized by abnormal signal transduction mechanisms in T lymphocytes. Linker for activation of T cells (LAT) couples TCR/CD3 activation with downstream signaling pathways. We reported diminished ERK 1/2 kinase activity in TCR/CD3 stimulated lupus T cells. In this study we evaluated the expression, phosphorylation, lipid raft and immunological synapse (IS) localization and colocalization of LAT with key signalosome molecules. We observed a diminished expression and an abnormal localization of LAT in lipid rafts and at the IS in activated lupus T cells. LAT phosphorylation, capture by GST-Grb2 fusion protein, and coupling to Grb2 and PLCγ1, was similar in healthy control and lupus T cells. Our results suggest that an abnormal localization of LAT within lipid rafts and its accelerated degradation after TCR/CD3 activation may compromise the assembly of the LAT signalosome and downstream signaling pathways required for full MAPK activation in lupus T cells.
authors.affiliation: Centro Nacional de Enfermedades Reumáticas, Division of Rheumatology, Hospital Universitario de Caracas, Universidad Central de Venezuela, Ciudad Universitaria, Caracas, Venezuela. nursamaa@yahoo.com
authors.forename: Nursamaa
authors.initials: N
authors.lastname: Abdoel
authors.forename: Susana
authors.initials: S
authors.lastname: Brun
authors.forename: Carmen
authors.initials: C
authors.lastname: Bracho
authors.forename: Martín A
authors.initials: MA
authors.lastname: Rodríguez
authors.forename: Ana M
authors.initials: AM
authors.lastname: Blasini
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D010766:Phosphorylation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D017260:Receptor-CD3 Complex, Antigen, T-Cell