Src Homology Phosphotyrosyl Phosphatase 2 (SHP2)

SHP2 is a non-receptor protein tyrosine phosphatase encoded by the PTPN11 gene. It plays a crucial role in various cell signaling pathways, including RAS/MAPK, PI3K/AKT, and JAK/STAT, regulating cell growth, proliferation, and differentiation. SHP2 consists of two SH2 domains (N-SH2 and C-SH2), a PTP catalytic domain, and a C-terminal tail. Its activity is regulated by auto-inhibition, where the N-SH2 domain blocks the PTP active site. Binding of phosphorylated ligands to the N-SH2 relieves this inhibition, activating SHP2. Mutations in PTPN11/SHP2 are implicated in several diseases, including Noonan syndrome, LEOPARD syndrome, hematologic malignancies, and solid tumors. Due to its central role in cancer-related signaling, SHP2 has emerged as an important drug target, with inhibitors targeting allosteric sites under development for cancer therapy.

Other names

PTPN11SH-PTP2Protein tyrosine phosphatase non-receptor type 11

Allosteric inhibition of SHP2