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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

The tyrosine phosphatase Shp2 in development and cancer

Katja S Grossmann1, Marta Rosário, Carmen Birchmeier

  • 1Department of Cancer Research, Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany.

Advances in Cancer Research
|April 20, 2010
PubMed

Insights

Shp2 tyrosine phosphatase mutations cause developmental disorders like Noonan syndrome and cancers such as juvenile myelomonocytic leukemia. Understanding Shp2's role in signaling pathways is key to disease mechanisms.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Shp2 tyrosine phosphatase regulates receptor tyrosine kinase (RTK) and cytokine receptor signaling.
  • Germline mutations in the PTPN11 gene (encoding Shp2) are linked to Noonan (NS) and LEOPARD syndromes.
  • Somatic Shp2 mutations are implicated in human malignancies, including juvenile myelomonocytic leukemia (JMML).

Purpose of the Study:

  • To elucidate the role of Shp2 in signaling pathways.
  • To understand the mechanisms of Shp2 in embryonic development and tumorigenesis.
  • To investigate the link between Shp2 mutations and human diseases.

Main Methods:

  • Analysis of germline and somatic mutations in the PTPN11 gene.
  • Utilizing animal models with conditional gain-of-function (GOF) and loss-of-function (LOF) Shp2 mutations.
  • Studying Shp2's function in receptor tyrosine kinase and cytokine receptor signaling pathways.

Main Results:

  • Gain-of-function (GOF) Shp2 mutations cause Noonan syndrome and JMML.
  • Loss-of-function (LOF) Shp2 mutations are associated with LEOPARD syndrome.
  • Animal models demonstrate Shp2's critical role in embryonic development and cellular transformation.

Conclusions:

  • Shp2 is a crucial regulator of signaling pathways involved in development and cancer.
  • Understanding Shp2's function is vital for developing therapies for Shp2-associated diseases.
  • Conditional mutation models provide insights into Shp2's dual role in development and disease.

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