The Rho-family GTP exchange factor Vav is a critical transducer of T cell receptor signals to the calcium, ERK, and NF-κB pathways

• DOI: 10.1073/pnas.96.6.3035
• Publication Date: 2002-07-26T14:39:15Z
• Authors: Patrick S. Costello; Alice E. Walters; P. Joseph Mee; Martin Turner; Lucinda F. Reynolds; Antonella Prisco; Nitza Sarner; Rose Zamoyska; Victor L. J. Tybu...
• Keywords: ZAP-70 Protein-Tyrosine Kinase; T-Lymphocytes; NF-kappa B; Receptors, Antigen, T-Cell; Cell Cycle Proteins; Protein-Tyrosine Kinases; GTP Phosphohydrolases; Mice; 03 medical and health sciences; 0302 clinical medicine; Lymphocyte Specific Protein Tyrosine Kinase p56(lck); Proto-Oncogene Proteins; Mutation; Animals; Calcium; Proto-Oncogene Proteins c-vav; Signal Transduction

Vav is a GTP/GDP exchange factor (GEF) for members of the Rho-family GTPases that rapidly tyrosine-phosphorylated after engagement T cell receptor (TCR), suggesting it may transduce signals from receptor. cells mice made Vav-deficient by gene targeting ( −/− ) fail to proliferate in response TCR stimulation because they secrete IL-2. We now show this due at least part failure initiate IL-2 transcription. Furthermore, we analyze TCR-proximal signaling pathways and despite normal activation Lck ZAP-70 tyrosine kinases, mutant have specific defects TCR-induced intracellular calcium fluxes, extracellular signal-regulated mitogen-activated protein kinases NF-κB transcription factor. Finally, greatly reduced flux an important cause their proliferative defect, restoration with ionophore reverses phenotype.