FIGURE 8. Model for proposed action of PTP-PEST in coupling membrane protrusion and tail retraction.

PTP-PEST functions at the front and back of a migrating cell. At the cell front PTP-PEST controls the extent of membrane protrusion. At the cell rear PTP-PEST is required for tail retraction. Excess PTP-PEST blocks membrane protrusion. The absence of PTP-PEST results in excessive protrusion, the formation of multiple leading edges, and a lack of tail retraction. PTP-PEST mediates its effect through reciprocally modulating the localized activity of Rac1 and RhoA through direct regulation of the activity and/or sub-cellular targeting of VAV2 and p190RhoGAP. ECM, extracellular cell matrix.