PTPN11 and cancer: It binds simultaneously to the interfaces of the N-SH2, C-SH2 and PTP structural domains of SHP2, creating hydrogen bonding interactions with key amino acid residues (Arg111, Phe113 and Glu250) and stabilizing SHP2 in a closed, self-inhibited conformation.288 This mechanism of action inhibits SHP2 activity through a metastable mechanism, leading to the inhibition of RAS/ERK signaling and suppressing RTK-driven proliferation of human cancer cells in vitro.286–288