DIRECT EVIDENCE OF INVOLVEMENT OF GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED PROTEINS IN THE HEAVY METAL-MEDIATED SIGNAL DELIVERY INTO T-LYMPHOCYTES

The biological significance of the action of glycosylphosphatidylinositol (GPI)-anchored proteins in cell physiology and pathology when stimulated with their natural agonists is not known, Here me provide evidence that GPI-anchored proteins play a crucial role in the recently defined heavy metal (HgCl2)-triggered signal delivery to T lymphocytes. Thiol-reactive HgCl2, a multi-potent crosslinker of cell membrane proteins, induced heavy aggregation of Thy-1, a representative GPI-anchored protein, on murine thymocytes, and delivered a signal to induce heavy tyrosine phosphorylation of cellular proteins, This rather unusual signal delivery by HgCl2 is diminished by the pre-treatment of cells,vith phosphatidylinositol-specific phospholipase C, which partially cleaved GPI-anchored proteins from the cell, surface, Direct evidence for the involvement of GPI or GPI-anchored proteins in the HgCl2-mediated signaling is provided by the loss of signaling in a mutant thymoma cell line defective in the phosphatidylinositol glycan-class A gene (PIG-A), and its restoration in a transfectant with PIG-A.