Jump to main content
Jump to site search

Issue 1, 2009
Previous Article Next Article

An integrated comparative phosphoproteomic and bioinformatic approach reveals a novel class of MPM-2 motifs upregulated in EGFRvIII-expressing glioblastoma cells

Author affiliations

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 tyrosinephosphorylation 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/threoninephosphorylation 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.

Graphical abstract: An integrated comparative phosphoproteomic and bioinformatic approach reveals a novel class of MPM-2 motifs upregulated in EGFRvIII-expressing glioblastoma cells

Back to tab navigation

Supplementary files

Publication details

The article was received on 29 Aug 2008, accepted on 15 Oct 2008 and first published on 30 Oct 2008


Article type: Paper
DOI: 10.1039/B815075C
Mol. BioSyst., 2009,5, 59-67

  •   Request permissions

    An integrated comparative phosphoproteomic and bioinformatic approach reveals a novel class of MPM-2 motifs upregulated in EGFRvIII-expressing glioblastoma cells

    B. A. Joughin, K. M. Naegle, P. H. Huang, M. B. Yaffe, D. A. Lauffenburger and F. M. White, Mol. BioSyst., 2009, 5, 59
    DOI: 10.1039/B815075C

Search articles by author

Spotlight

Advertisements