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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

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Regulation of bone and skeletal development by the SHP-2 protein tyrosine phosphatase

Nobuhiro Kamiya1, Harry K W Kim2, Philip D King3

  • 1Center for Excellence in Hip Disorders, Texas Scottish Rite Hospital for Children, Dallas, TX 75219, USA; Orthopaedic Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390-8883, USA; Sports Medicine, Tenri University, Tenri, Nara 632-0071, Japan.

Bone
|September 3, 2014
PubMed

Insights

Mutations in the PTPN11 gene, which encodes SHP-2, cause skeletal abnormalities in humans. Mouse studies reveal SHP-2

Area of Science:

  • Molecular Biology
  • Genetics
  • Developmental Biology

Background:

  • The PTPN11 gene encodes SHP-2, an intracellular signaling molecule crucial for cell growth and differentiation.
  • Germline mutations in PTPN11 are linked to human developmental disorders like Noonan and LEOPARD syndromes, which feature skeletal abnormalities.
  • SHP-2 also plays a role in benign bone tumors (metachondromatosis) and skeletal development, as shown in mouse models.

Purpose of the Study:

  • To review the significance of mouse gene targeting studies on SHP-2.
  • To understand the pathogenesis of skeletal abnormalities in humans with PTPN11 mutations.
  • To connect findings from mouse models to human skeletal diseases.

Main Methods:

  • Review of existing literature on PTPN11 mutations and SHP-2 function.
  • Analysis of gene targeting studies in mice related to skeletal development.
  • Comparison of mouse findings with human skeletal abnormalities in PTPN11-associated syndromes.

Main Results:

  • SHP-2 is essential for normal bone and skeletal development in mice.
  • Mouse studies provide insights into the mechanisms underlying skeletal defects in human PTPN11-related disorders.
  • SHP-2 signaling is a key regulator of skeletal growth and patterning.

Conclusions:

  • Mouse models are valuable for studying the pathogenesis of human skeletal abnormalities caused by SHP-2 mutations.
  • Understanding SHP-2's role in skeletal development can inform therapeutic strategies for related human diseases.
  • PTPN11 mutations have a significant impact on skeletal development across species.
Keywords:
Ras signalingSHP-2metachondromatosisscoliosisskeletal deformity

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