Linker for activation of T cells is displaced from lipid rafts and decreases in lupus T cells after activation via the TCR/CD3 pathway

Academic Article


  • 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. © 2011 Elsevier Inc.
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    Author List

  • Abdoel N; Brun S; Bracho C; Rodríguez MA; Blasini AM
  • Start Page

  • 243
  • End Page

  • 251
  • Volume

  • 142
  • Issue

  • 3