Vav and SLP-76 Interact and Functionally Cooperate in IL-2 Gene Activation

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 Jurk...

Full description

Saved in:
Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 1996-06, Vol.4 (6), p.593-602
Main Authors: Wu, Jun, Motto, David G, Koretzky, Gary A, Weiss, Arthur
Format: Article
Language:English
Subjects:
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(00)80485-9