T-cell and basophil activation through the cytoplasmic tail of T-cell-receptor zeta family proteins.
The zeta chain of the T-cell antigen receptor is the prototype of a family of proteins that exist as disulfide-linked dimers and are subunits of the T-cell antigen receptor and both IgE and IgG binding Fc receptors. Two related genes encode the zeta and gamma proteins. In this study we examine the ability of chimeric proteins consisting of the extracellular domain of the alpha chain of the interleukin 2 receptor (Tac) and the cytoplasmic domain of either zeta or gamma to activate cells when expressed in either T cells or rat basophilic leukemia cells. The zeta and gamma chimera were effective at eliciting interleukin 2 production in T cells and serotonin release in rat basophilic leukemia cells when externally cross-linked. Cytoplasmic-tail deletion mutants of zeta and gamma were constructed and used to verify the specificity of cell activation by these chimeric proteins. Signaling potencies of complementary mutants having the zeta tail truncated in position 108 or deleted from positions 66 through 114 suggested the presence of several functional domains in zeta.
Letourneur
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Cell Biology and Metabolism Branch, National Institute of Child Health and Development, National Institutes of Health, Bethesda, MD 20892.
Klausner
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D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001491:Basophils / Q000276:immunology*; D002460:Cell Line; D002678:Chimera; D004247:DNA / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D015183:Restriction Mapping; D012701:Serotonin / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; C054979:antigen T cell receptor, zeta chain; D012701:Serotonin; D004247:DNA