PathwayStep6514 PathwayStep6513 PathwayStep6511 PathwayStep6512 PathwayStep6510 PathwayStep6509 Activation of PAK by Rac1 and Cdc42 Activation of Rac1 by pVav1 Activation of Cdc42 by pVav1 Translocation of Vav1 to CD28 Activation of Vav1 Grb2 binds CD28 CD28 dependent Vav1 pathway Authored: Garapati, P V, 2008-12-16 11:12:19 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.<br>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. Edited: Garapati, P V, 2008-12-16 11:12:19 Pubmed10849438 Pubmed12670394 Pubmed15886116 Reactome Database ID Release 43389359 Reactome, http://www.reactome.org ReactomeREACT_19238 Reviewed: Bluestone, JA, Esensten, J, 2009-06-01 18:47:33