Reference Report

Reference
Citation	Friedman, A.A., Tucker, G., Singh, R., Yan, D., Vinayagam, A., Hu, Y., Binari, R., Hong, P., Sun, X., Porto, M., Pacifico, S., Murali, T., Finley, R.L., Asara, J.M., Berger, B., Perrimon, N. (2011). Proteomic and functional genomic landscape of receptor tyrosine kinase and ras to extracellular signal-regulated kinase signaling. Sci. Signal. 4(196): rs10. (Export to RIS)
FlyBase ID	FBrf0216513
Publication Type	Research paper
PubMed ID	22028469
PubMed 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.
DOI	10.1126/scisignal.2002029
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Sci. Signal.
Title	Science signaling
Publication Year
ISBN/ISSN	1937-9145
Data from Reference
Alleles (69)
	ACC^TR00325A.1 ago^HM04005 Arc42^GD11398 Arc42^KK100761 aret^HM04010 Axn^HM04012 brm^HM04019 cact^HM04020 Caf1^HM04021 Cap-G^HM04022 Cdc27^HM04024 CG3332^HM04052 CG3523^GD14739 CG3523^HM05141 CG3523^KK107330 CG3523^NIG.3523R CG5844^GD11787 CG5844^HM04057 CG6453^GD5314 CG6453^KK101779 CG6907^{dsRNA.Scer\UAS.WIZ} CG6984^HM04063 CG8963^HM04067 CG13298^HM04033 CG34422^{dsRNA.Scer\UAS.WIZ} CG34422^HM04064 chinmo^HM04048 chinmo^{Scer\UAS.T:Ivir\HA1} Chro^GD7070 Chro^KK105370 Chro^NIG.10712-1R CoRest^HM04053 CTPsyn^HM04062 dco^{Scer\UAS.T:Ivir\HA1} dgt2^HM04038 Dref^GD11784 Dref^JF02232 fzy^HM04081 hyx^HM04031 IntS3^HM04039 kis^NIG.3696R Not1^{dsRNA.Scer\UAS.WIZ} Not1^{Scer\UAS.T:Ivir\HA1} PpV^KK108896 PpV^NIG.12217R Ras85D^N17.Scer\UAS Rbp^{Scer\UAS.T:Ivir\HA1} Rtf1^HM04026 Scer\GAL4^ap-md544 Scer\GAL4^Bx-MS1096 Scer\GAL4^ey.PU sl^GD1535 sl^HMS00377 sl^HMS00695 sl^KK101565 Spc105R^HM04030 Spn42Dc^HM04068 Tep4^GD5530 Tep4^KK106228 Tpc1^HM04059 uex^KK114110 uri^HM04028 Vha100-5^TRiP.cUa Vps4^HM04061 wah^{dsRNA.Scer\UAS.WIZ} αTub85E^HM04009 β'Cop^HM04017 βCop^HM04016 δCOP^HM04076
Constructs (16)
	P{NIG.3523R} P{NIG.10712-1R} P{NIG.12217R} P{TRiP.HM04010} P{TRiP.HM04022} P{TRiP.TR00325A.1} P{TRiP.Vha100-5.U} P{UAS-CG6907.WIZ} P{UAS-CG34422.WIZ} P{UAS-chinmo.HA} P{UAS-dco.HA} P{UAS-Not1.HA} P{UAS-Ras85D.N17} P{UAS-Rbp.HA} P{UAS-sco.WIZ} P{UAS-wah.WIZ}
Genes (94)
	ACC ago Akt1 Arc42 aret Axn brm bru-2 cact Caf1 Cap-G cdc2c Cdc27 CG3332 CG3523 CG5346 CG5844 CG6453 CG6907 CG6984 CG7288 CG7324 CG8389 CG8963 CG9468 CG10916 CG13298 CG15060 CG34422 CG43894 chinmo Chro cnk CoRest csw CTPsyn dco dgt2 dos Dref drk Dsor1 Egfr eIF4AIII fzy gig hyx InR IntS3 kis ksr mago Not1 phl PpV PRL-1 Pten PTP-ER puc Pvr Ras85D RasGAP1 Rbp rl RpL6 RpL23A RpL27 RpS18 RpS30 RSG7 Rtf1 Scer\GAL4 skd sl Snap Socs36E Sos Spc105R Spn42Dc Src42A T:Ivir\HA1 Tak1 Tep4 Tor Tpc1 uex uri Vha100-5 Vps4 wah αTub85E β'Cop βCop δCOP
Insertions (2)
	P{GawB}ap^md544 P{GawB}Bx^MS1096
Natural transposons (1)
	P-element