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An integrated comparative phosphoproteomic and bioinformatic approach reveals a novel class of MPM-2 motifs upregulated in EGFRvIII-expressing glioblastoma cells.
- Source :
-
Molecular bioSystems [Mol Biosyst] 2009 Jan; Vol. 5 (1), pp. 59-67. Date of Electronic Publication: 2008 Oct 30. - Publication Year :
- 2009
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Abstract
- Glioblastoma (GBM, WHO grade IV) is an aggressively proliferative and invasive brain tumor that carries a poor clinical prognosis with a median survival of 9 to 12 months. In a prior phosphoproteomic study performed in the U87MG glioblastoma cell line, we identified tyrosine phosphorylation events that are regulated as a result of titrating EGFRvIII, a constitutively active mutant of the epidermal growth factor receptor (EGFR) associated with poor prognosis in GBM patients. In the present study, we have used the phosphoserine/phosphothreonine-specific antibody MPM-2 (mitotic protein monoclonal #2) to quantify serine/threonine phosphorylation events in the same cell lines. By employing a bioinformatic tool to identify amino acid sequence motifs regulated in response to increasing oncogene levels, a set of previously undescribed MPM-2 epitope sequence motifs orthogonal to the canonical "pS/pT-P" motif was identified. These motifs contain acidic amino acids in combinations of the -5, -2, +1, +3, and +5 positions relative to the phosphorylated amino acid. Phosphopeptides containing these motifs are upregulated in cells expressing EGFRvIII, raising the possibility of a general role for a previously unrecognized acidophilic kinase (e.g. casein kinase II (CK2)) in cell proliferation downstream of EGFR signaling.
- Subjects :
- Amino Acid Motifs
Antibody Specificity
Antigens chemistry
Antigens immunology
Cell Line, Tumor
Computational Biology
Humans
Phosphoproteins chemistry
Phosphoproteins metabolism
Antibodies immunology
ErbB Receptors metabolism
Glioblastoma immunology
Glioblastoma metabolism
Phosphoproteins analysis
Phosphoproteins immunology
Up-Regulation
Subjects
Details
- Language :
- English
- ISSN :
- 1742-2051
- Volume :
- 5
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular bioSystems
- Publication Type :
- Academic Journal
- Accession number :
- 19081932
- Full Text :
- https://doi.org/10.1039/b815075c