Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Vav1: a key signal transducer downstream of the TCR.

Immunological reviews | 2003

Vav1 is a 95-kDa protein expressed in all hemopoietic cells that becomes rapidly tyrosine phosphorylated following T cell antigen receptor (TCR) stimulation. Vav1 contains multiple domains characteristic of signal transducing proteins, including a Dbl homology domain, a hallmark of a guanine nucleotide exchange factor (GEF) for Rho-family GTPases. Indeed Vav1 is a GEF for Rac1, Rac2 and RhoG, and it is activated following tyrosine phosphorylation. Generation of mice deficient in Vav1 has shown that it plays an important role in selection events within the thymus, including both positive and negative selection, consistent with Vav1 transducing TCR signals required to drive these processes. Furthermore, Vav1-deficient T cells are defective in TCR-induced proliferation and cytokine synthesis. Analysis of TCR signaling pathways in Vav1-deficient T cells and thymocytes has shown that Vav1 is required to transduce signals to the activation of a calcium flux, extracellular signal-regulated kinase (ERK) and the nuclear factor kappaB (NF-kappaB) transcription factor. Vav1 has also been shown to control the activation of phospholipase Cgamma1 (PLCgamma1) via both phosphoinositide-3-kinase (PI3K)-dependent and -independent pathways. Finally, Vav1 has been shown to transduce TCR signals to some but not all cytoskeleton-dependent pathways. In particular, Vav1 is required for efficient TCR-induced conjugate formation with antigen presenting cells (APCs), activation of the integrin leukocyte function-associated antigen-1 (LFA-1) and cell polarization.

Pubmed ID: 12670394 RIS Download

Mesh terms: Animals | Cell Cycle Proteins | Cell Lineage | Cytoskeleton | Humans | Mice | Models, Immunological | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-vav | Receptors, Antigen, T-Cell | Signal Transduction | T-Lymphocytes