A phosphoproteomic analysis of the ErbB2 receptor tyrosine kinase signaling pathways.
Overexpression of the ErbB2 receptor tyrosine kinase is common in human cancers and is associated with an increased level of metastasis. To better understand the cellular signaling networks activated by ErbB2, a phosphoproteomic analysis of tyrosine-phosphorylated proteins was carried out in ErbB2-overexpressing breast and ovarian cancer cell lines. A total of 153 phosphorylation sites were assigned on 78 proteins. Treatment of cells with Herceptin, a monoclonal antibody that inhibits ErbB2 activity, significantly reduced the number of detectable protein phosphorylation sites, suggesting that many of these proteins participate in ErbB2-driven cell signaling. Of the 71 proteins that were differentially phosphorylated, only 13 were previously reported to directly associate with ErbB2. The differentially phosphorylated proteins included kinases, adaptor/docking proteins, proteins involved in cell proliferation and migration, and several uncharacterized RNA binding proteins. Selective depletion of some of these proteins, including RNA binding proteins SRRM2, SFRS1, SFRS9, and SFRS10, by siRNAs reduced the rate of migration of ErbB2-overexpressing ovarian cancer cells.
Mukherji
Mridul
M
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Brill
Laurence M
LM
Ficarro
Scott B
SB
Hampton
Garret M
GM
Schultz
Peter G
PG
D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002853:Chromatography, Liquid; D006801:Humans; D008969:Molecular Sequence Data; D010748:Phosphopeptides / Q000032:analysis; D010750:Phosphoproteins / Q000032:analysis*; D010766:Phosphorylation; D040901:Proteomics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry* / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D010748:Phosphopeptides; D010750:Phosphoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases