Related Experiment Video

Updated: Aug 13, 2026

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

Shp2 as a therapeutic target for leptin resistance and obesity

Gen-Sheng Feng1

  • 1Program in Signal Transduction, The Burnham Institute for Medical Research, La Jolla, CA 92037, USA. gfeng@burnham.org

Expert Opinion on Therapeutic Targets
|January 31, 2006
PubMed

Insights

Leptin resistance is common in obesity. The protein Shp2 enhances leptin signaling, suggesting that boosting Shp2 activity could be a new strategy for treating obesity and leptin resistance.

Area of Science:

  • Neuroendocrinology
  • Molecular signaling pathways
  • Metabolic disease research

Background:

  • Leptin resistance limits obesity treatment options.
  • Understanding leptin signaling is key for developing new therapies.
  • The tyrosine phosphatase Shp2 is implicated in leptin signaling.

Purpose of the Study:

  • To investigate the role of Shp2 in leptin signaling and energy balance.
  • To explore Shp2 as a potential therapeutic target for obesity and leptin resistance.

Main Methods:

  • Analysis of leptin signaling pathways (LepRb-STAT3, ERK).
  • Phenotypic characterization of mice with neuron-specific Shp2 deletion.
  • Review of experimental data on Shp2 function in metabolism.

Main Results:

  • Shp2 modulates leptin's effects on hypothalamic energy balance.
  • Shp2 downregulates the LepRb-STAT3 pathway but enhances ERK activation.
  • Mice lacking Shp2 in forebrain neurons exhibit obesity and hyperleptinemia.

Conclusions:

  • Shp2 acts as a leptin signal enhancer.
  • Pharmaceutical enhancement of Shp2 activity presents a potential therapeutic strategy for leptin resistance and obesity.

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