Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2.
T cell activation stimulates p56(lck), p59(fyn), ZAP-70, Vav-SLP-76 binding, and IL-2 transcription. Major questions concern the tyrosine-kinase and relevant site(s) needed for Vav-SLP-76 complex formation and its role in IL-2 production. Here, we show that of the three kinases, only ZAP-70 phosphorylates SLP-76 at specific sites that allow Vav SH2 ... domain binding. Therefore, while p56(lck) regulates proximal events, ZAP-70 acts downstream on targets such as SLP-76. We also show by in vitro and in vivo analysis that two SLP-76 pYESP motifs (Y113 and Y128) mediate binding, the first being more efficient. A third pYEPP motif (Y145) failed to bind. Finally, TCR zeta CD3 ligation of T cell hybridoma DC27.10 induces IL-2 production without detectable Vav-SLP-76 binding. Therefore, despite effects of Vav-SLP-76 on IL-2 expression, Vav-SLP-76 binding per se is not essential for IL-2 production in all T cells.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Cell Line, Humans, Interleukin-2, Jurkat Cells, Membrane Proteins, Mice, Molecular Sequence Data, Oncogene Proteins, Phosphoproteins, Protein Binding, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-vav, Receptor-CD3 Complex, Antigen, T-Cell, Receptors, Antigen, T-Cell, T-Lymphocytes, ZAP-70 Protein-Tyrosine Kinase
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Cell Line, Humans, Interleukin-2, Jurkat Cells, Membrane Proteins, Mice, Molecular Sequence Data, Oncogene Proteins, Phosphoproteins, Protein Binding, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-vav, Receptor-CD3 Complex, Antigen, T-Cell, Receptors, Antigen, T-Cell, T-Lymphocytes, ZAP-70 Protein-Tyrosine Kinase
Immunity
Date: Feb. 01, 1997
PubMed ID: 9047237
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