Vav and SLP-76 interact and functionally cooperate in IL-2 gene activation

Immunity. 1996 Jun;4(6):593-602. doi: 10.1016/s1074-7613(00)80485-9.

Abstract

T cell antigen receptor (TCR) stimulation induces tyrosine phosphorylation of many intracellular proteins, including the proto-oncogene Vav, which is expressed exclusively in hematopoietic and trophoblast cells. Vav is critical for lymphocyte development and activation. Overexpression of Vav in Jurkat T cells leads to potentiation of TCR-mediated IL-2 gene activation. However, the biochemical function of Vav is unknown. Here, we demonstrate that the major induced tyrosine phosphoprotein associated with Vav is the hematopoietic cell-specific SLP-76. The Vav SH2 domain is required for this interaction and for TCR-mediated Vav tyrosine phosphorylation. Similar to Vav, overexpression of SLP-76 markedly potentiates TCR-mediated NF-AT and IL-2 gene activation. Furthermore, overexpression of both Vav and SLP-76 synergistically induces basal and TCR-stimulated NF-AT activation. These results suggest that a signaling complex containing Vav and SLP-76 plays an important role in lymphocyte activation.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Gene Expression Regulation / immunology*
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Interleukin-2 / genetics*
  • Leukemia, T-Cell
  • Oncogene Proteins / metabolism*
  • Oncogene Proteins / physiology
  • Phosphoproteins / metabolism*
  • Phosphoproteins / physiology
  • Phosphorylation
  • Protein-Tyrosine Kinases / immunology
  • Proto-Oncogene Proteins c-vav
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Transcriptional Activation
  • Tumor Cells, Cultured

Substances

  • Adaptor Proteins, Signal Transducing
  • Interleukin-2
  • Oncogene Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins c-vav
  • SLP-76 signal Transducing adaptor proteins
  • VAV1 protein, human
  • Protein-Tyrosine Kinases