PloS one, 2013-03, Vol.8 (3), p.e55657-e55657
2013
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Protein phosphorylation profiling using an in situ proximity ligation assay: phosphorylation of AURKA-elicited EGFR-Thr654 and EGFR-Ser1046 in lung cancer cells
- Ist Teil von
- PloS one, 2013-03, Vol.8 (3), p.e55657-e55657
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The epidermal growth factor receptor (EGFR), which is up-regulated in lung cancer, involves the activation of mitogenic signals and triggers multiple signaling cascades. To dissect these EGFR cascades, we used 14 different phospho-EGFR antibodies to quantify protein phosphorylation using an in situ proximity ligation assay (in situ PLA). Phosphorylation at EGFR-Thr654 and -Ser1046 was EGF-dependent in the wild-type (WT) receptor but EGF-independent in a cell line carrying the EGFR-L858R mutation. Using a ProtoAarray™ containing ∼5000 recombinant proteins on the protein chip, we found that AURKA interacted with the EGFR-L861Q mutant. Moreover, overexpression of EGFR could form a complex with AURKA, and the inhibitors of AURKA and EGFR decreased EGFR-Thr654 and -Ser1046 phosphorylation. Immunohistochemical staining of stage I lung adenocarcinoma tissues demonstrated a positive correlation between AURKA expression and phosphorylation of EGFR at Thr654 and Ser1046 in EGFR-mutant specimens, but not in EGFR-WT specimens. The interplay between EGFR and AURKA provides an explanation for the difference in EGF dependency between EGFR-WT and EGFR-mutant cells and may provide a new therapeutic strategy for lung cancer patients carrying EGFR mutations.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0055657Titel-ID: cdi_plos_journals_1330881216
- Format
- –
- Schlagworte
- Adenocarcinoma, Adenocarcinoma - enzymology, Adenocarcinoma - genetics, Adenocarcinoma - pathology, Antibodies, Antibodies - chemistry, Aurora Kinase A, Aurora Kinases, Biology, Cancer, Cancer therapies, Cascades, Cell cycle, Cell Line, Tumor, Clinical medicine, Epidermal growth factor, Epidermal growth factor receptors, Epidermal growth factors, Female, Gene amplification, Gene expression, Health aspects, HEK293 Cells, Hospitals, Humans, Immunoglobulins, Immunohistochemistry, Immunohistochemistry - methods, Kinases, Laboratories, Ligands, Lung cancer, Lung diseases, Lung Neoplasms - enzymology, Lung Neoplasms - genetics, Lung Neoplasms - pathology, Male, Medical prognosis, Medicine, Mutation, Phosphorylation, Phosphorylation - genetics, Protein Array Analysis - methods, Protein-Serine-Threonine Kinases - genetics, Protein-Serine-Threonine Kinases - metabolism, Proteins, Receptor, Epidermal Growth Factor - genetics, Receptor, Epidermal Growth Factor - metabolism, Recombinant proteins, Rodents, Science, Signal transduction, Signaling, Thoracic surgery, Tissues, Tumor necrosis factor-TNF