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Insulin regulates heregulin binding and ErbB3 expression in rat hepatocytes
R S Carver1, M X Sliwkowski, S Sitaric
1Department of Pediatrics, Vanderbilt University, theVanderbilt Cancer Center, Nashville, Tennessee 37232, USA. California 94080, USA.
The Journal of Biological Chemistry
|June 7, 1996
Summary
The heregulin-ErbB system impacts liver cells, with insulin inhibiting heregulin beta-1 (HRGbeta1) binding to ErbB3 receptors. This interaction regulates liver cell growth and function, potentially linking to the animal
Area of Science:
- Cell biology
- Molecular endocrinology
- Hepatocyte signaling
Background:
- The heregulin-ErbB system comprises novel ligands and receptors related to epidermal growth factor (EGF).
- These proteins regulate critical cellular processes including growth, differentiation, and gene expression across various cell types.
Purpose of the Study:
- To identify and characterize the heregulin beta-1 (HRGbeta1) receptor on cultured rat hepatocytes.
- To investigate the influence of insulin on HRGbeta1 binding and signaling in these cells.
Main Methods:
- Radioligand binding assays using a labeled EGF domain peptide of HRGbeta1.
- Cross-linking experiments to identify receptor interactions.
- Measurement of DNA synthesis, receptor phosphorylation, and protein levels.
Main Results:
- HRGbeta1 significantly stimulated hepatocyte DNA synthesis.
- HRGbeta1 specifically bound to ErbB3 receptors, inducing its phosphorylation and reducing its protein levels.
- Insulin inhibited HRGbeta1 binding to ErbB3 receptors and reduced the number of binding sites.
- HRGbeta1 binding and ErbB3 levels increased in cultured hepatocytes over time, requiring de novo protein synthesis.
Conclusions:
- The heregulin-ErbB system plays a role in regulating liver cell functions.
- Insulin modulates HRGbeta1 signaling in hepatocytes, suggesting a link to metabolic and nutritional status.