piperidines and Noonan-Syndrome

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.

Topics: Cerebrosides; Depsipeptides; Gain of Function Mutation; Humans; LEOPARD Syndrome; Loss of Function Mutation; Molecular Targeted Therapy; Noonan Syndrome; Phosphoric Monoester Hydrolases; Piperidines; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Pyrimidines; Signal Transduction