p-5Y-LAT:PLCG1:GADS:p-Y113,Y128,Y145-SLP-76 p-5Y-LAT:PLCG1:GADS:p-3Y-SLP-76:BTK:VAV VAV2/VAV3 Recruitment of VAV and BTK to p-SLP-76 Authored: Garapati, P V, 2012-05-25 Edited: Garapati, P V, 2012-05-25 Pubmed10934226 Pubmed12640123 Pubmed15365099 Pubmed21659545 Reactome Database ID Release 432424481 Reactome, http://www.reactome.org ReactomeREACT_147785 Reviewed: Lanier, Lewis L, 2012-08-09 VAV2 and VAV3 are expressed in human NK cells and play a central role in NK cell-mediated cytotoxicity. They are required for DAP12-mediated signaling; their loss profoundly impairs DAP12-induced cytotoxicity (Billadeau et al. 2000, Cella et al. 2004). Phosphorylated SLP-76 tyrosines Y113 and Y128 provide binding sites for the SH2 domains of VAV. The binding of VAV to these phosphotyrosine residues may link SLP-76 to the Jun amino-terminal kinase (JNK) pathway and the actin cytoskeleton. Y145 has been implicated in the binding of SLP-76 to the Tec family kinase BTK (Kettner et al. 2003). BTK is required for secretion of pro-inflammatory cytokines, phosphorylation of ERK1/2 and PLCgamma and Ca2+ mobilization (Ormsby et al. 2010).