Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer

被引：1947

作者：

Rikova, Klarisa ^{[1
]}

Guo, Ailan ^{[1
]}

Zeng, Qingfu ^{[1
]}

Possemato, Anthony ^{[1
]}

Yu, Jian ^{[1
]}

Haack, Herbert ^{[1
]}

Nardone, Julie ^{[1
]}

Lee, Kimberly ^{[1
]}

Reeves, Cynthia ^{[1
]}

Li, Yu ^{[1
]}

Hu, Yerong ^{[3
]}

Tan, Zhiping ^{[3
]}

Stokes, Matthew ^{[1
]}

Sullivan, Laura ^{[1
]}

Mitchell, Jeffrey ^{[1
]}

Wetzel, Randy ^{[1
]}

MacNeill, Joan ^{[1
]}

Ren, Jian Min ^{[1
]}

Yuan, Jin ^{[1
]}

Bakalarski, Corey E. ^{[2
]}

Villen, Judit ^{[2
]}

Kornhauser, Jon M. ^{[1
]}

Smith, Bradley ^{[1
]}

Li, Daiqiang ^{[1
,4
]}

Zhou, Xinmin ^{[3
]}

Gygi, Steven P. ^{[2
]}

Gu, Ting-Lei ^{[1
]}

Polakiewicz, Roberto D. ^{[1
]}

Rush, John ^{[1
]}

Comb, Michael J. ^{[1
]}

机构：

[1] Cell Signaling Technol, Danvers, MA 01923 USA

[2] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[3] Cent S Univ, Xiangya Hosp 2, Dept Cardiothorac Surg, Changsha 410011, Hunan, Peoples R China

[4] Cent S Univ, Xiangya Hosp 2, Dept Pathol, Changsha 410011, Hunan, Peoples R China

来源：

CELL | 2007年 / 131卷 / 06期

关键词：

D O I：

10.1016/j.cell.2007.11.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Despite the success of tyrosine kinase-based cancer therapeutics, for most solid tumors the tyrosine kinases that drive disease remain unknown, limiting our ability to identify drug targets and predict response. Here we present the first large-scale survey of tyrosine kinase activity in lung cancer. Using a phosphoproteomic approach, we characterize tyrosine kinase signaling across 41 non-small cell lung cancer (NSCLC) cell lines and over 150 NSCLC tumors. Profiles of phosphotyrosine signaling are generated and analyzed to identify known oncogenic kinases such as EGFR and c-Met as well as novel ALK and ROS fusion proteins. Other activated tyrosine kinases such as PDGFR alpha and DDR1 not previously implicated in the genesis of NSCLC are also identified. By focusing on activated cell circuitry, the approach outlined here provides insight into cancer biology not available at the chromosomal and transcriptional levels and can be applied broadly across all human cancers.

引用

页码：1190 / 1203

页数：14

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