Mammalian PTPases can be subdivided into two broad categories: transmembrane receptor PTPases and intracellular PTPases. SHP-2 (PTPN11) is one of the 2 closely related mammalian intracellular PTPases whose sequences encode 2 tandem SRC homology 2 (SH2) domains located at the N-terminal side and a single PTPase catalytic domain at C-terminus. In the inactive state, the N-terminal SH2 domain interacts with the PTP catalytic domain and blocks access of potential substrates to the active site. Upon binding to target phospho-tyrosyl residues, the N-terminal SH2 domain is released from the PTP domain, and the enzyme is activated by relieving this autoinhibition. SHP-2 is widely expressed in most tissues and plays a regulatory role in various cell signaling events that are important for a diversity of cell functions, such as mitogenic activation, metabolic control, transcription regulation, and cell migration.