Reactome | CD28 dependent Vav1 pathway

CD28 dependent Vav1 pathway

Stable Identifier

R-HSA-389359

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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CD28 binds to several intracellular proteins including PI3 kinase, Grb-2, Gads and ITK. Grb-2 specifically co-operates with Vav-1 in the up-regulation of NFAT/AP-1 transcription. CD28 costimulation resulted in a prolonged and sustained phosphorylation and membrane localization of Vav1 in comparison to T-cell receptor activation alone. Tyrosine-phosphorylated Vav1 is an early point of integration between the signaling routes triggered by the T-cell receptor and CD28.
Vav1 transduces TCR and co-stimulatory signals to multiple biochemical pathways and several cytoskeleton-dependent processes. The products of Vav1 activation, Rac1 and Cdc42, in turn activate the mitogen-activated protein kinases JNK and p38. Vav1 is also required for TCR-induced calcium flux, activation of the ERK MAP kinase pathway, activation of the NF-kB transcription factor, inside-out activation of the integrin LFA-1, TCR clustering, and polarisation of the T cell.

Literature References

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