Reactome | Activation of Vav1

Activation of Vav1

Stable Identifier

R-HSA-389354

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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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 Michel, F, Grimaud, L, Tuosto, L, Acuto, O	J Biol Chem	1998
12670394	Vav1: a key signal transducer downstream of the TCR Tybulewicz, VL, Ardouin, L, Prisco, A, Reynolds, LF	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 Hehner, SP, Hofmann, TG, Dienz, O, Droge, W, Schmitz, ML	J Biol Chem	2000
15886116	Vav-family proteins in T-cell signalling Tybulewicz, VL	Curr Opin Immunol	2005