Figure 6

Model of CTLA-4 induced T-cell unresponsiveness. 1. In resting T cells (left panel) PAG restricts mobility of the lipid rafts and recruits Csk to the membrane, where it blocks activation of the Src family kinases. 2. In the absence of PAG (right panel) Fyn activity is increased, resulting in enhanced proximal signaling events. 3. However, at a later time point enhanced Fyn activity also leads to hyper-phosphorylation of CTLA-4. 4. Phosphorylated CTLA-4 can recruit the protein tyrosine phosphatase Shp-1 to the lipid rafts, where Shp-1 blocks T-cell activation by inactivating ZAP-70.