Phosphoproteome of signaling by ErbB2 in ovarian cancer cells.

Abstract

The gene for receptor tyrosine kinase ErbB2 is amplified in breast and ovarian tumours. The linear pathway by which signals are transduced through ErbB2 are well known. However, second generation questions that address spatial aspects of signaling remain. To address this, we have undertaken a mass spectrometry approach to identify phosphoproteins specific for ErbB2 using the inhibitors Lapatinib and CP724714 in ovarian cancer cells. The ErbB2 specific proteins identified in SKOV-3 cells were Myristoylated alanine-rich C-kinase substrate, Protein capicua homolog, Protein peptidyl isomerase G, Protein PRRC2C, Chromobox homolog1 and PRP4 homolog. We have evaluated three phosphoproteins PKM2, Aldose reductase and MARCKS in SKOV-3 cells. We observed that PKM2 was phosphorylated by EGF but was not inhibited by Lapatinib and CP724714. The activity of aldose reductase in reducing NADPH as a substrate was significantly higher in EGF stimulated cells which was inhibited by Lapatinib and CP724714 but not by Geftinib (EGFR inhibitor). MARCKS was phosphorylated on stimulation of SKOV-3 cells with EGF that was inhibited by Lapatinib and CP724714 which was dependent on the kinase activity of ErbB2. These results have identified phosphoproteins that are specific to ErbB2 which have not been previously reported and sets the basis for future experiments.

• Authors: C Sidhanth, S Bindhya, S Krishnapriya, P Manasa, A Shabna, J Alifia, C Patole, V Kumar, M Garg, T S Ganesan
• Journal: Biochimica et biophysica acta. Proteins and proteomics (Biochim Biophys Acta Proteins Proteom) Vol. 1870 Issue 4 Pg. 140768 (04 01 2022) ISSN: 1878-1454 [Electronic] Netherlands
• PMID: 35158093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Phosphoproteins
• Lapatinib
• Epidermal Growth Factor
• Aldehyde Reductase
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Aldehyde Reductase
• Cell Line, Tumor
• Epidermal Growth Factor
• Female
• Humans
• Lapatinib (pharmacology)
• Ovarian Neoplasms
• Phosphoproteins (metabolism)
• Receptor, ErbB-2