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Sequestosome 1/p62, a scaffolding protein, is a newly identified partner of IRS-1 protein

Thangiah Geetha1, Chen Zheng, Nilmini Vishwaprakash

  • 1Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL 36849, USA.

The Journal of Biological Chemistry
|July 5, 2012
PubMed

Insights

Sequestosome 1/p62 protein interacts with insulin receptor substrate-1, improving glucose uptake and insulin signaling. This finding is crucial for understanding and treating metabolic syndrome and type 2 diabetes.

Area of Science:

  • Molecular Biology
  • Cellular Metabolism
  • Endocrinology

Background:

  • Insulin resistance in skeletal muscle is an early sign of metabolic syndrome and a precursor to type 2 diabetes.
  • Defects in insulin signaling are implicated in the development of insulin resistance.
  • Sequestosome 1/p62 (p62) protein deficiency in mice leads to obesity, insulin resistance, and type 2 diabetes.

Purpose of the Study:

  • To investigate the role of sequestosome 1/p62 (p62) in the insulin-signaling pathway.
  • To elucidate the interaction between p62 and insulin receptor substrate-1 (IRS-1).

Main Methods:

  • Utilized mapping studies to identify the interaction domain between p62 and IRS-1.
  • Examined the effect of p62 overexpression on key insulin signaling components and cellular processes.

Main Results:

  • The SH(2) domain of p62 interacts with IRS-1 upon insulin stimulation.
  • IRS-1 binds to p62 via specific YMXM motifs, similar to its interaction with phosphoinositol 3-kinase.
  • Overexpression of p62 enhanced Akt phosphorylation, GLUT4 translocation, and glucose uptake.

Conclusions:

  • p62 plays a significant role in the insulin-signaling pathway.
  • p62 mediates insulin signaling through its interaction with IRS-1.
  • Targeting the p62-IRS-1 interaction may offer therapeutic strategies for insulin resistance and type 2 diabetes.

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