Phosphorylation of multiple CD3 zeta tyrosine residues leads to formation of pp21 in vitro and in vivo. Structural changes upon T cell receptor stimulation
| Autor: | S, Koyasu, D J, McConkey, L K, Clayton, S, Abraham, B, Yandava, T, Katagiri, P, Moingeon, T, Yamamoto, E L, Reinherz |
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| Rok vydání: | 1992 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte Hybridomas Base Sequence CD3 Complex Macromolecular Substances T-Lymphocytes Molecular Sequence Data Receptors Antigen T-Cell Antibodies Monoclonal Transfection Cell Line Mice Oligodeoxyribonucleotides Mutagenesis Site-Directed Animals Interleukin-2 Tyrosine Amino Acid Sequence Phosphorylation Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 267(5) |
| ISSN: | 0021-9258 |
| Popis: | T lymphocyte activation resulting from antigen recognition involves a protein tyrosine kinase pathway which triggers phosphorylation of several cellular substrates including the CD3 zeta subunit of the T cell receptor (TCR) to form pp21. The homologous TCR-associated protein, CD3 eta, is an alternatively spliced product of the same gene locus as CD3 zeta. CD3 eta lacks one of six cytoplasmic tyrosine residues (Tyr-132) found in CD3 zeta and is itself not phosphorylated. Site-directed mutagenesis in conjunction with in vitro and in vivo phosphorylation studies herein demonstrates that Tyr-132 is required for the formation of pp21. Moreover, the differential phosphorylation of CD3 zeta versus CD3 eta is not due to a selective association of the known TCR-associated protein tyrosine kinase, p59fyn; p59fyn but not p56lck or p62yes is associated with each of the three TCR isoforms containing CD3 zeta 2, or CD3 eta 2, or CD3 zeta-eta. This association occurs through components of the TCR complex distinct from CD3 zeta or CD3 eta. In addition, we show that pp21 formation is not only dependent on Tyr-132 but results from concomitant phosphorylation of other CD3 zeta residues including Tyr-121. Mutation of Tyr-90, -121, or -132 does not alter primary signal transduction as shown by the ability of individual CD3 zeta Tyr----Phe mutants to produce interleukin-2 upon TCR stimulation. Thus, the substantial structural changes in CD3 zeta upon TCR stimulation as reflected by alteration in its mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis may affect subsequent events such as receptor desensitization, receptor movement, and/or protein associations. |
| Databáze: | OpenAIRE |
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