Proteome-wide Tyrosine Phosphorylation Analysis Reveals Dysregulated Signaling Pathways in Ovarian Tumors.
Mol Cell Proteomics
; 18(3): 448-460, 2019 03.
Article
en En
| MEDLINE
| ID: mdl-30523211
ABSTRACT
The recent accomplishment of comprehensive proteogenomic analysis of high-grade serous ovarian carcinoma (HGSOC) tissues reveals cancer associated molecular alterations were not limited to variations among DNA, and mRNA/protein expression, but are a result of complex reprogramming of signaling pathways/networks mediated by the protein and post-translational modification (PTM) interactomes. A systematic, multiplexed approach interrogating enzyme-substrate relationships in the context of PTMs is fundamental in understanding the dynamics of these pathways, regulation of cellular processes, and their roles in disease processes. Here, as part of Clinical Proteomic Tumor Analysis Consortium (CPTAC) project, we established a multiplexed PTM assay (tyrosine phosphorylation, and lysine acetylation, ubiquitylation and SUMOylation) method to identify protein probes' PTMs on the human proteome array. Further, we focused on the tyrosine phosphorylation and identified 19 kinases are potentially responsible for the dysregulated signaling pathways observed in HGSOC. Additionally, elevated kinase activity was observed when 14 ovarian cancer cell lines or tumor tissues were subjected to test the autophosphorylation status of PTK2 (pY397) and PTK2B (pY402) as a proxy for kinase activity. Taken together, this report demonstrates that PTM signatures based on lysate reactions on human proteome array is a powerful, unbiased approach to identify dysregulated PTM pathways in tumors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Tirosina
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Proteínas Tirosina Quinasas
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Cistadenocarcinoma Seroso
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Proteómica
Límite:
Female
/
Humans
Idioma:
En
Revista:
Mol Cell Proteomics
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2019
Tipo del documento:
Article