| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3257165 | Clinical Immunology | 2012 | 9 Pages |
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.
► TCR/CD3 stimulated SLE T lymphocytes. ► Diminished LAT expression and abnormal lipid raft/immunological synapse localization. ► LAT phosphorylation and GST–Grb2 capture is similar to healthy controls. ► LAT coupling to Grb2 and PLCγ1 is conserved in both groups. ► Abnormal assembly of LAT signalosome may lead to faulty MAPK activation.
