Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2

Immunity. 1997 Feb;6(2):155-64. doi: 10.1016/s1074-7613(00)80422-7.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Humans
  • Interleukin-2 / biosynthesis*
  • Interleukin-2 / metabolism*
  • Jurkat Cells
  • Membrane Proteins / immunology*
  • Mice
  • Molecular Sequence Data
  • Oncogene Proteins / drug effects*
  • Oncogene Proteins / metabolism*
  • Phosphoproteins / drug effects*
  • Phosphoproteins / metabolism*
  • Protein Binding / drug effects
  • Protein-Tyrosine Kinases / pharmacology*
  • Proto-Oncogene Proteins c-vav
  • Receptor-CD3 Complex, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • ZAP-70 Protein-Tyrosine Kinase


  • Adaptor Proteins, Signal Transducing
  • Interleukin-2
  • Membrane Proteins
  • Oncogene Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins c-vav
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Receptors, Antigen, T-Cell
  • SLP-76 signal Transducing adaptor proteins
  • VAV1 protein, human
  • Vav1 protein, mouse
  • antigen T cell receptor, zeta chain
  • Protein-Tyrosine Kinases
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human
  • Zap70 protein, mouse