Title | An integrated comparative phosphoproteomic and bioinformatic approach reveals a novel class of MPM-2 motifs upregulated in EGFRvIII-expressing glioblastoma cells. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Joughin, BA, Naegle, KM, Huang, PH, Yaffe, MB, Lauffenburger, DA, White, FM |
Journal | Mol Biosyst |
Volume | 5 |
Issue | 1 |
Pagination | 59-67 |
Date Published | 2009 Jan |
ISSN | 1742-2051 |
Keywords | Amino Acid Motifs, Antibodies, Antibody Specificity, Antigens, Cell Line, Tumor, Computational Biology, Glioblastoma, Humans, Phosphoproteins, Receptor, Epidermal Growth Factor, Up-Regulation |
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. |
DOI | 10.1039/b815075c |
Alternate Journal | Mol Biosyst |
PubMed ID | 19081932 |
PubMed Central ID | PMC2701618 |
Grant List | R01 CA096504-07 / CA / NCI NIH HHS / United States R01 CA096504-09 / CA / NCI NIH HHS / United States R01 CA118705-01A2 / CA / NCI NIH HHS / United States R01 GM060594-08 / GM / NIGMS NIH HHS / United States R01-CA96504 / CA / NCI NIH HHS / United States R01-GM60594 / GM / NIGMS NIH HHS / United States U54 CA112967-05 / CA / NCI NIH HHS / United States U54-CA112967 / CA / NCI NIH HHS / United States |