CD28 dependent Vav1 pathway

Stable Identifier
R-HSA-389359
Type
Pathway
Species
Homo sapiens
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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
10849438 Tyrosine-phosphorylated Vav1 as a point of integration for T-cell receptor- and CD28-mediated activation of JNK, p38, and interleukin-2 transcription

Hehner, SP, Hofmann, TG, Dienz, O, Droge, W, Schmitz, ML

J Biol Chem 2000
12670394 Vav1: a key signal transducer downstream of the TCR

Tybulewicz, VL, Ardouin, L, Prisco, A, Reynolds, LF

Immunol Rev 2003
15886116 Vav-family proteins in T-cell signalling

Tybulewicz, VL

Curr Opin Immunol 2005
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