Reactome | Recruitment of VAV and BTK to p-SLP-76

Recruitment of VAV and BTK to p-SLP-76

Stable Identifier

R-HSA-2424481

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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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. 2011).

Literature References

PubMed ID	Title	Journal	Year
21659545	Btk is a positive regulator in the TREM-1/DAP12 signaling pathway Ormsby, T, Schlecker, E, Ferdin, J, Tessarz, AS, Angelisová, P, Köprülü, AD, Borte, M, Warnatz, K, Schulze, I, Ellmeier, W, Horejsí, V, Cerwenka, A	Blood	2011
15365099	Differential requirements for Vav proteins in DAP10- and ITAM-mediated NK cell cytotoxicity Cella, M, Fujikawa, K, Tassi, I, Kim, S, Latinis, K, Nishi, S, Yokoyama, W, Colonna, M, Swat, W	J. Exp. Med.	2004