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Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

PTPN11 is the first identified proto-oncogene that encodes a tyrosine phosphatase

Rebecca J Chan1, Gen-Sheng Feng

  • 1Department of Pediatrics, the Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, USA.

Blood
|October 21, 2006
PubMed

Insights

The PTPN11 gene, encoding the tyrosine phosphatase Shp2, is identified as a proto-oncogene. Its gain-of-function mutations are linked to leukemia and cancer by activating the Ras-Erk pathway.

Area of Science:

  • Molecular biology
  • Cancer research
  • Genetics

Background:

  • Carcinogenesis research relies on identifying oncogenes and tumor suppressor genes.
  • The protein tyrosine phosphatase, PTPN11, plays a crucial role in normal hematopoiesis.

Purpose of the Study:

  • To identify PTPN11 as the first proto-oncogene encoding a cytoplasmic tyrosine phosphatase with SH2 domains.
  • To investigate the role of PTPN11 mutations in cancer development.

Main Methods:

  • Identification and characterization of PTPN11.
  • Detection of somatic missense mutations in PTPN11.
  • Analysis of the Ras-Erk pathway activation.

Main Results:

  • PTPN11 was identified as a proto-oncogene encoding Shp2, a tyrosine phosphatase with two SH2 domains.
  • Somatic missense PTPN11 gain-of-function mutations were found in leukemias and some solid tumors.
  • These mutations lead to aberrant hyperactivation of the Ras-Erk pathway.

Conclusions:

  • PTPN11 is a key player in cell transformation and a significant finding in cancer research.
  • Understanding PTPN11's role offers new insights into the molecular mechanisms of leukemia and cancer.

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