Phosphatidylinositol-based glycolipid-anchored proteins enhance proximal TCR signaling events.
Previous reports suggested that T lymphocyte activation through phosphatidylinositol-based glycolipid (GPI)-anchored molecules is dependent on surface expression of the TCR. Here we show that stimulation of the TCR in five mutant cell lines with deficiencies in GPI biosynthesis fails to induce tyrosine phosphorylation of the TCR zeta-chain and ZAP-70, indicating that early events in TCR-mediated signal transduction are affected in these mutants. The Src kinases Fyn and Lck coprecipitating with activated TCR complexes are significantly less kinase active in the GPI-processing mutants than in wild-type cells. These data suggest that GPI-anchored proteins may play an important role in the initiation of TCR signal transduction by contributing to the accumulation of Src kinase activity in the TCR complex.
Romagnoli
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Institute of Biochemistry, B.I.L. Biomedical Research Center, University of Lausanne, Epalinges, Switzerland.
Bron
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D002460:Cell Line; D017261:Glycosylphosphatidylinositols / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D009154:Mutation; D009363:Neoplasm Proteins; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase; D019061:src-Family Kinases / Q000378:metabolism
D017261:Glycosylphosphatidylinositols; D009363:Neoplasm Proteins; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C092830:FRK protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D019061:src-Family Kinases