Genomic dissection of receptor tyrosine kinase activation of extracellular signal-regulated kinase in Drosophila

Adam Amiel Friedman

Receptor tyrosine kinase (RTK) signalling through extracellular signal-regulated kinases (ERKs) plays pivotal roles in development and disease, most notably in oncogenic transformation. While the core signalling cassette has been extensively investigated, this pathway is likely regulated by a larger network of moderate, context-specific proteins. To obtain a global view of RTK/ERK signalling, we performed a genome-wide RNAi screen in Drosophila cells using a quantitative cellular assay monitoring ERK activation. We show that ERK pathway output integrates a wide array of conserved cellular processes. Further analysis of selected components in multiple cell types with different RTK ligands validates and classifies 331 pathway regulators, several of which also demonstrate activity in vivo . The relevance of these genes is highlighted by our isolation of a novel Ste20-like kinase and...