Activation of Vav1

Stable Identifier
Reaction [transition]
Homo sapiens
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Vav1 exists in an auto-inhibitory state folded in such a way as to inhibit the GEF activity of its DH domain. This folding is mediated through binding of tyrosines in the acidic domain to the DH domain and through binding of the CH domain to the C1 region. Activation of Vav may involve at least three different events to relieve this auto-inhibition. Phosphorylation of the tyrosines causes them to be displaced from the DH domain, binding of a ligand to the CH domain may cause it to release the C1 domain and PIP3 may bind to the PH domain, altering its conformation. Vav1 is phosphorylated on at least three tyrosines (Y142, Y160 and Y174) in the acidic domain, and this phosphorylation results in an increase in GEF activity. Fyn tyrosine kinase phosphorylates Vav1 after CD28 ligation.
Literature References
PubMed ID Title Journal Year
9822663 Fyn and ZAP-70 are required for Vav phosphorylation in T cells stimulated by antigen-presenting cells

Acuto, O, Tuosto, L, Michel, F, Grimaud, L

J Biol Chem 1998
12670394 Vav1: a key signal transducer downstream of the TCR

Ardouin, L, Tybulewicz, VL, Reynolds, LF, Prisco, A

Immunol Rev 2003
10849438 Tyrosine-phosphorylated Vav1 as a point of integration for T-cell receptor- and CD28-mediated activation of JNK, p38, and interleukin-2 transcription

Hofmann, TG, Hehner, SP, Dienz, O, Schmitz, ML, Droge, W

J Biol Chem 2000
15886116 Vav-family proteins in T-cell signalling

Tybulewicz, VL

Curr Opin Immunol 2005
Catalyst Activity

protein tyrosine kinase activity of FYN [cytosol]

Orthologous Events
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