Vav1 bound to PIP3 and Grb2:CD28 pVav1:PIP3:Grb2:CD28 Activation of Vav1 Authored: Garapati, P V, 2008-12-16 11:12:19 EC Number: 2.7.10 Edited: Garapati, P V, 2008-12-16 11:12:19 Pubmed10849438 Pubmed12670394 Pubmed15886116 Pubmed9822663 Reactome Database ID Release 43389354 Reactome, http://www.reactome.org ReactomeREACT_19316 Reviewed: Bluestone, JA, Esensten, J, 2009-06-01 18:47:33 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. has a Stoichiometric coefficient of 3