p-VAV1,2,3 exchange 6TGTP for GDP on RAC1

Stable Identifier
R-HSA-9751201
Type
Reaction [transition]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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The guanine nucleotide exchange factors 1-3 (VAV1,2,3) act as guanine nucleotide exchange factors (GEFs) for Ras-related C3 botulinum toxin substrate (RAC1), catalysing the exchange of bound GDP for GTP (Heo et al. 2005, Jaiswal et al. 2013). To be fully active, VAV proteins are tyrosine-phosphorylated (Teramoto et al. 1997).

One of the active metabolites of azathioprine (6-thioguanosine triphosphate, 6TGTP) can block RAC1 activity by binding to it instead of GTP (presumably mediated by VAV proteins), thus converting a costimulatory signal into an apoptotic signal (Tiede et al. 2003).
Literature References
PubMed ID Title Journal Year
12697733 CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes

Ahmadian, MR, Fritz, G, Galle, PR, Becker, C, Wirtz, S, Walczak, H, Strand, S, Lehr, HA, Iven, H, Holtmann, M, Mudter, J, Bartsch, B, Tiede, I, Poppe, D, Hildner, K, Dvorsky, R, Neurath, MF, Strand, D, Blumberg, R, Atreya, R

J Clin Invest 2003
15850391 Recognition and activation of Rho GTPases by Vav1 and Vav2 guanine nucleotide exchange factors

Campbell, SL, Thapar, R, Heo, J

Biochemistry 2005
9099726 Tyrosine phosphorylation of the vav proto-oncogene product links FcepsilonRI to the Rac1-JNK pathway

Bustelo, XR, Salem, P, Teramoto, H, Gutkind, JS, Robbins, KC

J. Biol. Chem. 1997
23096567 New insight into the molecular switch mechanism of human Rho family proteins: shifting a paradigm

Ahmadian, MR, Jaiswal, M, Fansa, EK, Dvorsky, R

Biol. Chem. 2013
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Event Information
Catalyst Activity

guanyl-nucleotide exchange factor activity of p-VAV family [cytosol]

Orthologous Events
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