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Updated: Jul 25, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Peroxovanadate induces tyrosine phosphorylation of multiple signaling proteins in mouse liver and kidney
1Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
Abstract:
The intraperitoneal injection of a vanadate/H2O2 mixture (peroxovanadate) into mice resulted within minutes in the appearance of numerous tyrosine-phosphorylated proteins in the liver and kidney. These effects are presumably due to the inhibition of phosphotyrosine phosphatase activity. Three of the tyrosine-phosphorylated proteins have been identified as the receptors for epidermal growth factor, insulin, and hepatocyte growth factor. The injection of peroxovanadate also enhanced the tyrosine phosphorylation of many of the proteins known to function downstream of these receptors, including SHC, signal transducer and activator of transcription (Stat) 1alpha,beta, Stat 3, Stat 5, phospholipase C-gamma, insulin receptor substrate 1, GTPase-activating protein, beta-catenin, gamma-catenin, p120cas, SHP-1, and SHP-2. The administration of peroxovanadate also induced nuclear translocation of a number of tyrosine-phosphorylated Stat proteins. In addition, the global effects on tyrosine phosphorylation permitted the detection of a number of novel intracellular protein interactions, including an association of Tyk2 with beta-catenin. The in situ administration of peroxovanadate may prove useful in the search for novel tyrosine-phosphorylated proteins and the identification of new interactions between previously identified tyrosine-phosphorylated substrates.
Insights
Peroxovanadate injection rapidly increases tyrosine phosphorylation in mouse liver and kidney by inhibiting phosphatases. This method aids in discovering new tyrosine-phosphorylated proteins and their interactions.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Tyrosine phosphorylation regulates critical cellular processes.
- Phosphotyrosine phosphatases (PTPs) control tyrosine phosphorylation levels.
- Inhibiting PTPs can reveal cellular signaling pathways.
Purpose of the Study:
- To investigate the in vivo effects of peroxovanadate on protein tyrosine phosphorylation.
- To identify novel tyrosine-phosphorylated proteins and their interactions.
- To assess peroxovanadate as a tool for studying tyrosine phosphorylation signaling.
Main Methods:
- Intraperitoneal injection of peroxovanadate into mice.
- Analysis of protein tyrosine phosphorylation in liver and kidney tissues.
- Identification of phosphorylated proteins using techniques like Western blotting and mass spectrometry (implied).
Main Results:
- Rapid and widespread increase in tyrosine phosphorylation in liver and kidney within minutes.
- Identification of phosphorylated receptors for epidermal growth factor, insulin, and hepatocyte growth factor.
- Enhanced phosphorylation of downstream signaling proteins (e.g., SHC, Stats, PLC-gamma, IRS-1).
- Nuclear translocation of tyrosine-phosphorylated Stat proteins.
- Discovery of novel protein interactions, such as Tyk2 with beta-catenin.
Conclusions:
- Peroxovanadate effectively inhibits phosphotyrosine phosphatase activity in vivo.
- This approach facilitates the identification of novel tyrosine-phosphorylated proteins.
- Peroxovanadate is a valuable tool for exploring intracellular protein interactions in signaling pathways.
