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Knock-down of LAR protein tyrosine phosphatase induces insulin resistance

Ann Mander1, Conrad P Hodgkinson, Graham J Sale

  • 1School of Biological Sciences, Biomedical Sciences Building, University of Southampton, Bassett Crescent East, Southampton, SO16 7PX, UK.

FEBS Letters
|May 18, 2005
PubMed

Insights

Leukocyte common antigen-related protein tyrosine phosphatase (LAR) regulates insulin signaling. LAR knockdown caused insulin resistance by inhibiting key pathways, revealing LAR as a vital regulator of insulin sensitivity.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Insulin receptor (IR) signaling is crucial for glucose homeostasis.
  • The role of protein tyrosine phosphatases in insulin signaling is not fully understood.
  • Leukocyte common antigen-related protein tyrosine phosphatase (LAR) is a potential regulator.

Purpose of the Study:

  • To investigate the role of LAR in insulin receptor signaling.
  • To determine if LAR regulates post-receptor insulin signaling pathways.

Main Methods:

  • Developed a small interfering RNA (siRNA) probe targeting LAR.
  • Performed LAR knockdown in relevant cell models.
  • Assessed insulin-induced activation of protein kinase B (PKB/Akt) and mitogen-activated protein kinases (MAPK).
  • Analyzed the phosphorylation status of the insulin receptor (IR) and insulin receptor substrate (IRS) proteins.

Main Results:

  • LAR knockdown resulted in post-receptor insulin resistance.
  • Insulin-induced activation of PKB/Akt and MAPK pathways was significantly inhibited by LAR knockdown.
  • Phosphorylation and dephosphorylation of IR and IRS proteins were not affected by LAR knockdown.

Conclusions:

  • LAR is a critical regulator of insulin signaling sensitivity.
  • LAR plays a key role in modulating the activity of post-receptor insulin signaling pathways.
  • The developed siRNA probe is a valuable tool for studying LAR function.

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