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

J Pharmacol Sci. 2020 Nov;144(3):139-146. doi: 10.1016/j.jphs.2020.06.002. Epub 2020 Aug 3.

Abstract

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.

Keywords: SHP2; phosphatase-independent function; tyrosine phosphatase.

Publication types

  • Review

MeSH terms

  • Cerebrosides
  • Depsipeptides
  • Gain of Function Mutation
  • Humans
  • LEOPARD Syndrome / genetics
  • Loss of Function Mutation
  • Molecular Targeted Therapy
  • Noonan Syndrome / genetics
  • Phosphoric Monoester Hydrolases* / metabolism
  • Piperidines
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / antagonists & inhibitors
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / physiology*
  • Pyrimidines
  • Signal Transduction / genetics

Substances

  • Cerebrosides
  • Depsipeptides
  • Piperidines
  • Pyrimidines
  • SHP099
  • fusaruside
  • trichomide A
  • Phosphoric Monoester Hydrolases
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11