Phosphatase-independent functions of SHP2 and its regulation by small molecule compounds

• Main Authors: Wenjie Guo, Qiang Xu
• Format: Article
• Language: English
• Published: Elsevier 2020-11-01
• Series: Journal of Pharmacological Sciences
• Subjects: SHP2; tyrosine phosphatase; phosphatase-independent function
• Online Access: http://www.sciencedirect.com/science/article/pii/S134786132030058X

SHP2 is a non-receptor protein tyrosine phosphatase encoded by the PTPN11 gene in human. Clinically, SHP2 has been identified as a causal factor of several diseases, such as Noonan syndrome, LEOPARD syndrome as well as myeloid malignancies. Interestingly, both loss-of-function and gain-of-function mutations occur in the PTPN11 gene. Analyses by biochemical and cell biological means as well as probing with small molecule compounds have demonstrated that SHP2 has both phosphatase-dependent and independent functions. In comparison with its phosphatase activity, the non-phosphatase-like function of SHP2 has not been well introduced or summarized. This review mainly focuses on the phosphatase-independent functions and its regulation by small molecule compounds as well as their use for disease therapy.