title: Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer.
abstract: 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 PDGFRalpha 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.
authors: Cell Signaling Technology, 3 Trask Lane, Danvers, MA 01923, USA.
authors: Klarisa
authors: K
authors: Rikova
authors: Ailan
authors: A
authors: Guo
authors: Qingfu
authors: Q
authors: Zeng
authors: Anthony
authors: A
authors: Possemato
authors: Jian
authors: J
authors: Yu
authors: Herbert
authors: H
authors: Haack
authors: Julie
authors: J
authors: Nardone
authors: Kimberly
authors: K
authors: Lee
authors: Cynthia
authors: C
authors: Reeves
authors: Yu
authors: Y
authors: Li
authors: Yerong
authors: Y
authors: Hu
authors: Zhiping
authors: Z
authors: Tan
authors: Matthew
authors: M
authors: Stokes
authors: Laura
authors: L
authors: Sullivan
authors: Jeffrey
authors: J
authors: Mitchell
authors: Randy
authors: R
authors: Wetzel
authors: Joan
authors: J
authors: Macneill
authors: Jian Min
authors: JM
authors: Ren
authors: Jin
authors: J
authors: Yuan
authors: Corey E
authors: CE
authors: Bakalarski
authors: Judit
authors: J
authors: Villen
authors: Jon M
authors: JM
authors: Kornhauser
authors: Bradley
authors: B
authors: Smith
authors: Daiqiang
authors: D
authors: Li
authors: Xinmin
authors: X
authors: Zhou
authors: Steven P
authors: SP
authors: Gygi
authors: Ting-Lei
authors: TL
authors: Gu
authors: Roberto D
authors: RD
authors: Polakiewicz
authors: John
authors: J
authors: Rush
authors: Michael J
authors: MJ
authors: Comb
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D050939:Gene Fusion; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D019000:Phosphotyrosine; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D020796:Receptor, Platelet-Derived Growth Factor alpha