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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.

Authors :
Joughin BA
Naegle KM
Huang PH
Yaffe MB
Lauffenburger DA
White FM
Source :
Molecular bioSystems [Mol Biosyst] 2009 Jan; Vol. 5 (1), pp. 59-67. Date of Electronic Publication: 2008 Oct 30.
Publication Year :
2009

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.

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