Phosphorylation and activation of VAV

Stable Identifier
R-HSA-2730841
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Phosphorylation of VAV stimulates its GEF activity for RAC1, and thus it plays an important role in linking FCERI to the RAC1-JNK pathway. VAV 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 calponin homology (CH) domain to the C1 region. Activation of VAV may involve three events which relieve this auto-inhibition: phosphorylation of tyrosines in the acidic domain 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; binding of the PI3K product PIP3 to the PH domain may alter its conformation (Aghazadeh et al. 2000). VAV is phosphorylated on tyrosine residue (Y174 in VAV1/172 in VAV2/173 in VAV3) in the acidic domain. This is mediated by SYK and Src-family tyrosine kinases (Deckert et al. 1996, Schuebel et al. 1998). Once activated, VAV is involved in the activation of RAC1, PAK1, MEK and ERK and cytokine production.

Literature References
PubMed ID Title Journal Year
10395673 Tyrosine phosphorylation of Vav stimulates IL-6 production in mast cells by a Rac/c-Jun N-terminal kinase-dependent pathway

Song, JS, Haleem-Smith, H, Arudchandran, R, Gomez, J, Scott, PM, Mill, JF, Tan, TH, Rivera, J

J. Immunol. 1999
8986718 Functional and physical interactions of Syk family kinases with the Vav proto-oncogene product

Deckert, M, Tartare-Deckert, S, Couture, C, Mustelin, T, Altman, A

Immunity 1996
11007481 Structural basis for relief of autoinhibition of the Dbl homology domain of proto-oncogene Vav by tyrosine phosphorylation

Aghazadeh, B, Lowry, WE, Huang, XY, Rosen, MK

Cell 2000
9099726 Tyrosine phosphorylation of the vav proto-oncogene product links FcepsilonRI to the Rac1-JNK pathway

Teramoto, H, Salem, P, Robbins, KC, Bustelo, XR, Gutkind, JS

J. Biol. Chem. 1997
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