Fig. 2.

Model for thiopurine-mediated immunosuppression. The guanine nucleotide exchange factor (GEF) Vav1 activates Rac1 by the exchange of GDP for GTP. The active thiopurine metabolite thio-GTP binds to Rac1 instead of GTP. This thio-GTP-bound Rac 1 (Rac1thio-GTP) induces T-cell apoptosis (by a decrease of Bcl-XL [anti-apoptotic signal]) via inhibition of Rac 1 activation in T cells. Active Rac1 also ensures de-phosphorylation of Ezrin–Radixin–Moesin (pERM) to ERM. GDP guanosine diphosphate, GTP guanosine triphosphate