Fig. 9.

Modes of action of phosphatase inhibitors and activators. a–d The four known types of SHP2 inhibitors have diverse mechanisms that target the catalytic pocket of SHP2, that target the allosteric site of SHP2, that directly degrade the SHP2 protein, or that block the interaction between SHP2 and its substrates. e–h The inhibitor or activators of PP2A, including e a PP2A catalytic inhibitor undergoing clinical trials; f inhibitor of its endogenous inhibitory protein; g direct activator of PP2A; h post-translational modification of PP2A (e.g., methylation and phosphorylation). i Noncompetitive inhibitors of PTP1B bind to a site consisting of the last 20 residues of the catalytic domain. j The antisense oligonucleotide inhibitor of PTP1B messenger RNA reduces the translation of PTP1B protein. k, l JMS-053 and BCI are allosteric inhibitors of PRL3 and DUSP1/6, respectively