Fig. 1

SHP2 genomic organization, protein structure and regulatory mechanisms. a Diagrams depicting the structure and functional N-SH2, C-SH2, and PTPase domains of SHP2 and its two tyrosyl residues Y542 and Y580 in the carboxy-terminal tail, which have signaling capability upon phosphorylation in response to certain stimuli. Note: →, in-frame exon; x, out-of-frame exon. Amino acid numbers for each exon and functional domain are marked on top and bottom, respectively. b Crystallographic structure demonstrating the closed and autoinhibited state (left) and the open and active state (right) of SHP2. The active site (red) of the PTP domain (pink) is blocked by the N-SH2 domain (light blue). The C-SH2 domain is colored orange. Adapted with permission from ref. ³⁴ c Schematic model of SHP2 autoinhibition and activation. In the basal level, SHP2 is autoinhibited by the N-SH2 domain, blocking the active site. Upon binding to its signaling partners with its SH2 domains, an open and active conformation is established