RRC ID 15577
著者 Friedman AA, Tucker G, Singh R, Yan D, Vinayagam A, Hu Y, Binari R, Hong P, Sun X, Porto M, Pacifico S, Murali T, Finley RL Jr, Asara JM, Berger B, Perrimon N.
タイトル Proteomic and functional genomic landscape of receptor tyrosine kinase and ras to extracellular signal-regulated kinase signaling.
ジャーナル Sci Signal
Abstract Characterizing the extent and logic of signaling networks is essential to understanding specificity in such physiological and pathophysiological contexts as cell fate decisions and mechanisms of oncogenesis and resistance to chemotherapy. Cell-based RNA interference (RNAi) screens enable the inference of large numbers of genes that regulate signaling pathways, but these screens cannot provide network structure directly. We describe an integrated network around the canonical receptor tyrosine kinase (RTK)-Ras-extracellular signal-regulated kinase (ERK) signaling pathway, generated by combining parallel genome-wide RNAi screens with protein-protein interaction (PPI) mapping by tandem affinity purification-mass spectrometry. We found that only a small fraction of the total number of PPI or RNAi screen hits was isolated under all conditions tested and that most of these represented the known canonical pathway components, suggesting that much of the core canonical ERK pathway is known. Because most of the newly identified regulators are likely cell type- and RTK-specific, our analysis provides a resource for understanding how output through this clinically relevant pathway is regulated in different contexts. We report in vivo roles for several of the previously unknown regulators, including CG10289 and PpV, the Drosophila orthologs of two components of the serine/threonine-protein phosphatase 6 complex; the Drosophila ortholog of TepIV, a glycophosphatidylinositol-linked protein mutated in human cancers; CG6453, a noncatalytic subunit of glucosidase II; and Rtf1, a histone methyltransferase.
巻・号 4(196)
ページ rs10
公開日 2011-10-25
DOI 10.1126/scisignal.2002029
PII 4/196/rs10
PMID 22028469
PMC PMC3439136
MeSH Algorithms Animals Blotting, Western Cell Line Drosophila / cytology Drosophila / genetics Drosophila / metabolism Drosophila Proteins / genetics* Drosophila Proteins / metabolism* Extracellular Signal-Regulated MAP Kinases / genetics Extracellular Signal-Regulated MAP Kinases / metabolism Gene Regulatory Networks Genomics / methods* Immunoprecipitation MAP Kinase Signaling System* Models, Genetic Protein Binding Protein Interaction Mapping / methods Proteomics / methods* RNA Interference Receptor Protein-Tyrosine Kinases / genetics Receptor Protein-Tyrosine Kinases / metabolism Wings, Animal / growth & development Wings, Animal / metabolism ras Proteins / genetics ras Proteins / metabolism
IF 6.467
引用数 62
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
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