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Mol Cell Proteomics. 2018 Dec 6. pii: mcp.RA118.000851. doi: 10.1074/mcp.RA118.000851. [Epub ahead of print]

Proteome-wide tyrosine phosphorylation analysis reveals dysregulated signaling pathways in ovarian tumors.

Author information

1
Johns Hopkins School of Medicine, United States of America.
2
Johns Hopkins University School of Medicine, United States of America.
3
Pathology, Johns Hopkins School of Medicine.
4
Johns Hopkins, United States of America.
5
Johns Hopkins University.
6
Dept of Pharmacology & HiT Center, Johns Hopkins Medical Institute, United States of America hzhu4@jhmi.edu.

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. Furthermore, 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.

KEYWORDS:

CPTAC; Ovarian cancer; Phosphorylation; Protein array; Proteogenomics; Tyrosine Kinases*

PMID:
30523211
DOI:
10.1074/mcp.RA118.000851
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