Reference Report

Reference
Citation	Friedman, A., Perrimon, N. (2006). A functional RNAi screen for regulators of receptor tyrosine kinase and ERK signalling. Nature 444(7116): 230--234. (Export to RIS)
FlyBase ID	FBrf0194379
Publication Type	Research paper
PubMed ID	17086199
PubMed Abstract	Receptor tyrosine kinase (RTK) signalling through extracellular-signal-regulated kinases (ERKs) has pivotal roles during metazoan development, underlying processes as diverse as fate determination, differentiation, proliferation, survival, migration and growth. Abnormal RTK/ERK signalling has been extensively documented to contribute to developmental disorders and disease, most notably in oncogenic transformation by mutant RTKs or downstream pathway components such as Ras and Raf. Although the core RTK/ERK signalling cassette has been characterized by decades of research using mammalian cell culture and forward genetic screens in model organisms, signal propagation through this pathway is probably regulated by a larger network of moderate, context-specific proteins. The genes encoding these proteins may not have been discovered through traditional screens owing, in particular, to the requirement for visible phenotypes. To obtain a global view of RTK/ERK signalling, we performed an unbiased, RNA interference (RNAi), genome-wide, high-throughput screen in Drosophila cells using a novel, quantitative, cellular assay monitoring ERK activation. Here 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 and oncogenic stimuli-validates and classifies 331 pathway regulators. The relevance of these genes is highlighted by our isolation of a Ste20-like kinase and a PPM-family phosphatase that seem to regulate RTK/ERK signalling in vivo and in mammalian cells. Novel regulators that modulate specific pathway outputs may be selective targets for drug discovery.
DOI	10.1038/nature05280
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Nature
Title	Nature
Publication Year	1869-
ISBN/ISSN	0028-0836
Data from Reference
Aberrations (1)
	Df(3R)Exel6176
Alleles (20)
	Egfr^2.MtnA Egfr^E3 GckIII^{dsRNA.WIZ.Scer\UAS} GckIII^{K24R.Scer\UAS.T:Ivir\HA1} GckIII^{Scer\UAS.T:Ivir\HA1} Mmus\Cd8a^{Scer\UAS.T:Avic\GFP} mts^{Scer\UAS.T:Hsap\MYC} phl^{Scer\UAS.T:Hsap\MYC} Ppm1^{D228A.Scer\UAS.T:Ivir\HA1} Ppm1^{Scer\UAS.T:Ivir\HA1} Pvf1^cFa Ras85D^V12.MtnA Ras85D^V12.sev RasGAP1^B2 rl^{Scer\UAS.T:Avic\GFP-YFP} Scer\GAL4^ap-md544 Scer\GAL4^Bx-MS1096 Scer\GAL4^hs.2sev spi^s.MtnA T:Avic\GFP^YFP
Constructs (8)
	P{GAL4-Hsp70.sev} P{sevRas1.V12} P{UAS-GckIII.dsRNA.WIZ} P{UAS-GckIII.HA.K24R} P{UAS-GckIII.HA} P{UAS-mCD8::GFP.L} P{UAS-Ppm1.HA.D228A} P{UAS-Ppm1.HA}
Genes (61)
	AGO1 Akt1 ave B4 cact Cdk4 CG5844 CG6701 CG15060 CG42672 chico cnk CoRest csw CycA CycD CycE drk Dsor1 Egfr fz2 GckIII gig Hk InR Jra kay ksr l(2)NC136 Mmus\Cd8a mts nej Pdk1 phl Ppm1 Pten PTP-ER puc Pvf1 Pvr rad raptor Ras64B Ras85D RasGAP1 raw Rbp Rca1 Rheb rl S6k Scer\GAL4 SerT shn Sos spi T:Hsap\MYC T:Ivir\HA1 Tak1 Tor zfh1
Insertions (2)
	P{GawB}ap^md544 P{GawB}Bx^MS1096
Natural transposons (1)
	P-element