Fig. 8. Clustering and allosteric activation increase the activity of tethered SHP-1 by 900-fold.

(A) The concentration of SHP-1 experienced by the substrate when SHP-1 is tethered to clustered receptors (left), tethered to nonclustered receptors (center), and free in the cytoplasm (right). The concentration of SHP-1 increases 45-fold as it recruited from solution to clustered receptors. (B) The catalytic rate (${\mathit{k}}_{\text{cat}}^{*}$) increases 20-fold when SHP-1 is tethered (bound) to a receptor compared to when it is in solution. This allosteric activation of SHP-1 upon binding is consistent with a dynamic transition between closed low-activity and open high-activity states while in solution. The combination of increased concentration (45-fold) and increased catalytic activity (20-fold) leads to a 900-fold increase in the overall dephosphorylation rate because SHP-1 is recruited from solution to clustered receptors.