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

Guang Song, Li Chen, Bai Zhang, Qifeng Song, Yu Yu, Cedric Moore, Tian-Li Wang, Ie Ming Shih, Hui Zhang, Daniel Wan-Yui Chan, Zhen Zhang, Heng Zhu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)448-460
Number of pages13
JournalMolecular and Cellular Proteomics
Volume18
Issue number3
DOIs
StatePublished - Mar 1 2019

Fingerprint

Phosphorylation
Proteome
Post Translational Protein Processing
Pulse time modulation
Tyrosine
Tumors
Phosphotransferases
Tissue
Acetylation
Neoplasms
Proteins
Sumoylation
Carcinoma
Lysine
Ubiquitination
Assays
Proxy
Tumor Cell Line
Cells
Proteomics

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

Cite this

Proteome-wide tyrosine phosphorylation analysis reveals dysregulated signaling pathways in ovarian tumors. / Song, Guang; Chen, Li; Zhang, Bai; Song, Qifeng; Yu, Yu; Moore, Cedric; Wang, Tian-Li; Shih, Ie Ming; Zhang, Hui; Chan, Daniel Wan-Yui; Zhang, Zhen; Zhu, Heng.

In: Molecular and Cellular Proteomics, Vol. 18, No. 3, 01.03.2019, p. 448-460.

Research output: Contribution to journalArticle

@article{b193c0c53fec44ce8c44d138c6873a0b,
title = "Proteome-wide tyrosine phosphorylation analysis reveals dysregulated signaling pathways in ovarian tumors",
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.",
author = "Guang Song and Li Chen and Bai Zhang and Qifeng Song and Yu Yu and Cedric Moore and Tian-Li Wang and Shih, {Ie Ming} and Hui Zhang and Chan, {Daniel Wan-Yui} and Zhen Zhang and Heng Zhu",
year = "2019",
month = "3",
day = "1",
doi = "10.1074/mcp.RA118.000851",
language = "English (US)",
volume = "18",
pages = "448--460",
journal = "Molecular and Cellular Proteomics",
issn = "1535-9476",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "3",

}

TY - JOUR

T1 - Proteome-wide tyrosine phosphorylation analysis reveals dysregulated signaling pathways in ovarian tumors

AU - Song, Guang

AU - Chen, Li

AU - Zhang, Bai

AU - Song, Qifeng

AU - Yu, Yu

AU - Moore, Cedric

AU - Wang, Tian-Li

AU - Shih, Ie Ming

AU - Zhang, Hui

AU - Chan, Daniel Wan-Yui

AU - Zhang, Zhen

AU - Zhu, Heng

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85063009108&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063009108&partnerID=8YFLogxK

U2 - 10.1074/mcp.RA118.000851

DO - 10.1074/mcp.RA118.000851

M3 - Article

C2 - 30523211

AN - SCOPUS:85063009108

VL - 18

SP - 448

EP - 460

JO - Molecular and Cellular Proteomics

JF - Molecular and Cellular Proteomics

SN - 1535-9476

IS - 3

ER -