Raf

Summary

Gene Symbol: Raf
Description: Raf oncogene
Alias: 11-29, C110, CG2845, D-RAF, D-Raf, D-raf, D-raf1, DRaf, DRaf1, Dmel\CG2845, Draf, Draf-1, Draf1, EG:BACH48C10.3, Phl, RAF, Raf/phl, Raf1, dRaf, draf, l(1)2Fe, l(1)G0475, l(1)ph, l(1)phl, l(1)pole hole, l(1)polehole, l(1)polehole/draf, l(1)raf, lincRNA.937, ph1, phl, raf, raf-1, raf1, rafl, Raf oncogene, CG2845-PA, CG2845-PE, Raf-PA, Raf-PE, l(1)pole hole, pole hole, pole-hole, polehole, raf-like-oncogene-1
Species: fruit fly
Products:     Raf

Top Publications

  1. Jeon M, Zinn K. Receptor tyrosine phosphatases control tracheal tube geometries through negative regulation of Egfr signaling. Development. 2009;136:3121-9 pubmed publisher
    ..PTPRJ corresponds to the murine Scc1 (suppressor of colon cancer) gene. ..
  2. Almudi I, Stocker H, Hafen E, Corominas M, Serras F. SOCS36E specifically interferes with Sevenless signaling during Drosophila eye development. Dev Biol. 2009;326:212-23 pubmed publisher
    ..The SOCS family of adaptor proteins may have evolved as modulators of specific signaling pathways that contribute to the robustness and precision of cell fate specification. ..
  3. Perkins L, Larsen I, Perrimon N. corkscrew encodes a putative protein tyrosine phosphatase that functions to transduce the terminal signal from the receptor tyrosine kinase torso. Cell. 1992;70:225-36 pubmed
    ..by a signal transduction pathway that involves a receptor tyrosine kinase, torso, a serine/threonine kinase, D-raf, and the transcription factors, tailless and huckebein...
  4. Kurada P, White K. Ras promotes cell survival in Drosophila by downregulating hid expression. Cell. 1998;95:319-29 pubmed
    ..antiapoptotic activity in the developing eye is regulated by the Drosophila EGF receptor and operates through the Raf/MAPK pathway...
  5. Hipfner D, Cohen S. The Drosophila sterile-20 kinase slik controls cell proliferation and apoptosis during imaginal disc development. PLoS Biol. 2003;1:E35 pubmed
    ..Tumor-like tissue overgrowth results when apoptosis is prevented. We present evidence that Slik acts via Raf, but not via the canonical ERK pathway...
  6. Agaisse H, Perrimon N. The roles of JAK/STAT signaling in Drosophila immune responses. Immunol Rev. 2004;198:72-82 pubmed
  7. Uhlirova M, Bohmann D. JNK- and Fos-regulated Mmp1 expression cooperates with Ras to induce invasive tumors in Drosophila. EMBO J. 2006;25:5294-304 pubmed
  8. Martin Blanco E, Roch F, Noll E, Baonza A, Duffy J, Perrimon N. A temporal switch in DER signaling controls the specification and differentiation of veins and interveins in the Drosophila wing. Development. 1999;126:5739-47 pubmed
    ..Together, these temporal and spatial changes in the activity of DER constitute an autoregulatory network that controls the definition of vein and intervein cell types. ..
  9. Vidal M, Wells S, Ryan A, Cagan R. ZD6474 suppresses oncogenic RET isoforms in a Drosophila model for type 2 multiple endocrine neoplasia syndromes and papillary thyroid carcinoma. Cancer Res. 2005;65:3538-41 pubmed
    ..Our results support the view that targeting chemical kinase inhibitors such as ZD6474 to tissues with oncogenic forms of RET is a useful treatment strategy for RET-dependent carcinomas. ..

More Information

Publications64

  1. Yang L, Baker N. Cell cycle withdrawal, progression, and cell survival regulation by EGFR and its effectors in the differentiating Drosophila eye. Dev Cell. 2003;4:359-69 pubmed
    ..Each response requires the same Ras, Raf, MAPK, and Pnt signal transduction pathway...
  2. Sotillos S, de Celis J. Interactions between the Notch, EGFR, and decapentaplegic signaling pathways regulate vein differentiation during Drosophila pupal wing development. Dev Dyn. 2005;232:738-52 pubmed
    ..Once dpp expression is initiated, Dpp and EGFR activities in the provein maintain each other and, in cooperation, determine vein cell differentiation. ..
  3. Tong J, Schriner S, McCleary D, Day B, Wallace D. Life extension through neurofibromin mitochondrial regulation and antioxidant therapy for neurofibromatosis-1 in Drosophila melanogaster. Nat Genet. 2007;39:476-85 pubmed
    ..effects proved to be modulated by the adenylyl cyclase/cyclic AMP (cAMP)/protein kinase A pathway, not the Ras/Raf pathway. Treatment of wild-type D...
  4. Hou X, Chou T, Melnick M, Perrimon N. The torso receptor tyrosine kinase can activate Raf in a Ras-independent pathway. Cell. 1995;81:63-71 pubmed
    ..Previous analyses have demonstrated that Ras1 (p21ras) operates upstream of the D-Raf (Raf1) serine/threonine kinase in this signaling pathway...
  5. Brand A, Perrimon N. Raf acts downstream of the EGF receptor to determine dorsoventral polarity during Drosophila oogenesis. Genes Dev. 1994;8:629-39 pubmed
    In Drosophila, as in mammalian cells, the Raf serine/threonine kinase appears to act as a common transducer of signals from several different receptor tyrosine kinases...
  6. Baek K, Fabian J, Sprenger F, Morrison D, Ambrosio L. The activity of D-raf in torso signal transduction is altered by serine substitution, N-terminal deletion, and membrane targeting. Dev Biol. 1996;175:191-204 pubmed
    The Raf family of serine/threonine kinases are essential components in many receptor tyrosine kinase-mediated signal transduction pathways...
  7. Mishra S, Smolik S, Forte M, Stork P. Ras-independent activation of ERK signaling via the torso receptor tyrosine kinase is mediated by Rap1. Curr Biol. 2005;15:366-70 pubmed
    ..embryos, the Torso receptor tyrosine kinase (RTK) activates the small G protein Ras (D-Ras1) and the protein kinase Raf (D-Raf) to activate ERK to direct differentiation of terminal structures ...
  8. Chou T, Perrimon N. Use of a yeast site-specific recombinase to produce female germline chimeras in Drosophila. Genetics. 1992;131:643-53 pubmed
    ..We describe the parameters of FLP-recombinase induced germline mitotic recombination and the use of the "FLP-DFS" technique to analyze the maternal effect of X-linked zygotic lethal mutations. ..
  9. Casanova J, Llimargas M, Greenwood S, Struhl G. An oncogenic form of human raf can specify terminal body pattern in Drosophila. Mech Dev. 1994;48:59-64 pubmed
    ..Here, we show that a constitutively active form of human raf1 protein can trigger tll and hkb transcription in Drosophila embryos and specify elements of the terminal body ..
  10. Li J, Li W. Drosophila gain-of-function mutant RTK torso triggers ectopic Dpp and STAT signaling. Genetics. 2003;164:247-58 pubmed
    ..These results demonstrate an essential requirement of noncanonical signaling pathways for a persistently activated RTK to cause pathological defects in an organism. ..
  11. Rebay I, Chen F, Hsiao F, Kolodziej P, Kuang B, Laverty T, et al. A genetic screen for novel components of the Ras/Mitogen-activated protein kinase signaling pathway that interact with the yan gene of Drosophila identifies split ends, a new RNA recognition motif-containing protein. Genetics. 2000;154:695-712 pubmed
    ..We also isolated mutations in five previously uncharacterized genes, one of which, split ends, we have characterized molecularly and have shown to encode a member of the RRM family of RNA-binding proteins. ..
  12. Brumby A, Richardson H. scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila. EMBO J. 2003;22:5769-79 pubmed
  13. Li W, Skoulakis E, Davis R, Perrimon N. The Drosophila 14-3-3 protein Leonardo enhances Torso signaling through D-Raf in a Ras 1-dependent manner. Development. 1997;124:4163-71 pubmed
    14-3-3 proteins have been shown to interact with Raf-1 and cause its activation when overexpressed...
  14. Brunner D, Oellers N, Szabad J, Biggs W, Zipursky S, Hafen E. A gain-of-function mutation in Drosophila MAP kinase activates multiple receptor tyrosine kinase signaling pathways. Cell. 1994;76:875-88 pubmed
    ..Activation of MAP kinase by the rlSem mutation is both necessary and sufficient to activate multiple signaling pathways controlled by receptor tyrosine kinases. ..
  15. Anselmo A, Bumeister R, Thomas J, White M. Critical contribution of linker proteins to Raf kinase activation. J Biol Chem. 2002;277:5940-3 pubmed
    ..Here we show directly that CNK and KSR are required for stimulus dependent Raf kinase activation...
  16. Luo H, Rose P, Roberts T, Dearolf C. The Hopscotch Jak kinase requires the Raf pathway to promote blood cell activation and differentiation in Drosophila. Mol Genet Genomics. 2002;267:57-63 pubmed
    ..by activating multiple signaling pathways, including the Jak-Stat pathway, the PI3-kinase pathway, and the Ras/Raf pathway...
  17. Tsuda L, Inoue Y, Yoo M, Mizuno M, Hata M, Lim Y, et al. A protein kinase similar to MAP kinase activator acts downstream of the raf kinase in Drosophila. Cell. 1993;72:407-14 pubmed
    D-raf, a Drosophila homolog of Raf-1, plays key roles in multiple signal transduction pathways. Dsor1, a putative factor downstream of D-raf, was genetically identified by screening of dominant suppressors of D-raf...
  18. Roy F, Laberge G, Douziech M, Ferland McCollough D, Therrien M. KSR is a scaffold required for activation of the ERK/MAPK module. Genes Dev. 2002;16:427-38 pubmed
    ..In agreement with this, we found that KSR facilitates the phosphorylation of MEK by RAF. We further show that KSR associates independently with RAF and MEK, and that these interactions lead to the ..
  19. Prober D, Edgar B. Interactions between Ras1, dMyc, and dPI3K signaling in the developing Drosophila wing. Genes Dev. 2002;16:2286-99 pubmed
    ..Finally, we show that induction of dMyc and regulation of cell identity are separable effects of Raf/MAPK signaling...
  20. Ghiglione C, Carraway K, Amundadottir L, Boswell R, Perrimon N, Duffy J. The transmembrane molecule kekkon 1 acts in a feedback loop to negatively regulate the activity of the Drosophila EGF receptor during oogenesis. Cell. 1999;96:847-56 pubmed
    ..We show that the extracellular and transmembrane domains of Kek1 can inhibit and physically associate with the EGFR, suggesting potential models for this inhibitory mechanism. ..
  21. Schweitzer R, Howes R, Smith R, Shilo B, Freeman M. Inhibition of Drosophila EGF receptor activation by the secreted protein Argos. Nature. 1995;376:699-702 pubmed
    ..Thus the determination of cells by the DER pathway is regulated by a balance between extracellular activating and inhibiting signals. This is the first in vivo example of an extracellular inhibitor of a receptor tyrosine kinase. ..
  22. Therrien M, Morrison D, Wong A, Rubin G. A genetic screen for modifiers of a kinase suppressor of Ras-dependent rough eye phenotype in Drosophila. Genetics. 2000;156:1231-42 pubmed
    ..One of them corresponds to the kismet locus, which encodes a putative chromatin remodeling factor. The relevance of these loci with respect to the function of KSR and the Ras1 pathway in general is discussed. ..
  23. van der Straten A, Rommel C, Dickson B, Hafen E. The heat shock protein 83 (Hsp83) is required for Raf-mediated signalling in Drosophila. EMBO J. 1997;16:1961-9 pubmed
    ..cellular signalling proteins such as steroid hormone receptors, src-like kinases and the serine/threonine kinase Raf. While the interaction between steroid hormone receptors and Hsp90 appears to be essential for ligand binding and ..
  24. Matsuo T, Takahashi K, Kondo S, Kaibuchi K, Yamamoto D. Regulation of cone cell formation by Canoe and Ras in the developing Drosophila eye. Development. 1997;124:2671-80 pubmed
    ..The extra cone cells resulting from the interplay of Ras1v12 and Cno are generated from a pool of undifferentiated cells that are normally fated to develop into pigment cells or undergo apoptosis. ..
  25. Diaz Benjumea F, Hafen E. The sevenless signalling cassette mediates Drosophila EGF receptor function during epidermal development. Development. 1994;120:569-78 pubmed
    In Drosophila, Drk, an SH2 adaptor protein, Sos, a putative activator of Ras1, Ras1, raf and rolled/MAP kinase have been shown to be required for signalling from the sevenless and the torso receptor tyrosine kinase...
  26. Glise B, Noselli S. Coupling of Jun amino-terminal kinase and Decapentaplegic signaling pathways in Drosophila morphogenesis. Genes Dev. 1997;11:1738-47 pubmed
    ..Dorsal closure couples JNK and dpp signaling pathways, a situation that may be conserved in vertebrate development. ..
  27. Cutler R, Morrison D. Mammalian Raf-1 is activated by mutations that restore Raf signaling in Drosophila. EMBO J. 1997;16:1953-60 pubmed
    An interaction with the Ras proto-oncogene product is a requirement for Raf-1 activation in many signaling cascades...
  28. de Celis J. Expression and function of decapentaplegic and thick veins during the differentiation of the veins in the Drosophila wing. Development. 1997;124:1007-18 pubmed
  29. Karim F, Rubin G. Ectopic expression of activated Ras1 induces hyperplastic growth and increased cell death in Drosophila imaginal tissues. Development. 1998;125:1-9 pubmed
    ..Loss-of-function mutations in the genes encoding RAF, MEK, MAPK and KSR dominantly suppress RAS1V12-induced cell proliferation...
  30. Leptin M. Gastrulation in Drosophila: the logic and the cellular mechanisms. EMBO J. 1999;18:3187-92 pubmed
  31. Biggs W, Zavitz K, Dickson B, van der Straten A, Brunner D, Hafen E, et al. The Drosophila rolled locus encodes a MAP kinase required in the sevenless signal transduction pathway. EMBO J. 1994;13:1628-35 pubmed
    ..transduction pathway activated by Sev in the R7 precursor include proteins encoded by the gap1, drk, Sos, ras1 and raf loci...
  32. Li W, Melnick M, Perrimon N. Dual function of Ras in Raf activation. Development. 1998;125:4999-5008 pubmed
    ..We have used Drosophila embryos to examine the mechanism of Raf (Draf) activation in the complete absence of p21(Ras) (Ras1)...
  33. Lu X, Melnick M, Hsu J, Perrimon N. Genetic and molecular analyses of mutations involved in Drosophila raf signal transduction. EMBO J. 1994;13:2592-9 pubmed
    ..Ras binding region (CR1) of the Drosophila raf (D-raf) serine/threonine kinase. Four intragenic and seven extragenic suppressors were recovered...
  34. Karim F, Chang H, Therrien M, Wassarman D, Laverty T, Rubin G. A screen for genes that function downstream of Ras1 during Drosophila eye development. Genetics. 1996;143:315-29 pubmed
    ..Mutations in the Drosophila homologues of Raf, MEK, MAPK, type I Geranylgeranyl Transferase and Protein Phosphatase 2A were isolated, as were mutations in ..
  35. Laberge G, Douziech M, Therrien M. Src42 binding activity regulates Drosophila RAF by a novel CNK-dependent derepression mechanism. EMBO J. 2005;24:487-98 pubmed
    ..component of Drosophila receptor tyrosine kinase/mitogen-activated protein kinase pathways, regulates oppositely RAF function...
  36. Bergmann A, Agapite J, McCall K, Steller H. The Drosophila gene hid is a direct molecular target of Ras-dependent survival signaling. Cell. 1998;95:331-41 pubmed
    ..These findings define a novel mechanism by which growth factor signaling directly inactivates a critical component of the intrinsic cell death machinery. These studies provide further insights into the function of ras as an oncogene. ..
  37. Culi J, Martin Blanco E, Modolell J. The EGF receptor and N signalling pathways act antagonistically in Drosophila mesothorax bristle patterning. Development. 2001;128:299-308 pubmed
    ..among cells of the cluster that are mediated by the Epidermal growth factor receptor (EGFR) and the Ras/Raf pathway...
  38. Perrimon N. Signalling pathways initiated by receptor protein tyrosine kinases in Drosophila. Curr Opin Cell Biol. 1994;6:260-6 pubmed
    ..In addition to molecules previously identified from vertebrate studies, i.e. Grb2, Sos, Ras-Gap, p21ras, Raf, MEK and MAPK, genetic studies have suggested that two novel proteins, the protein tyrosine phosphatase (PTPase) ..
  39. O Keefe D, Prober D, Moyle P, Rickoll W, Edgar B. Egfr/Ras signaling regulates DE-cadherin/Shotgun localization to control vein morphogenesis in the Drosophila wing. Dev Biol. 2007;311:25-39 pubmed
    ..Ras, therefore, regulates both the transcriptional responses necessary for vein cell identity, and the cell adhesive changes that determine vein and intervein cell morphology. ..
  40. O Neill E, Rebay I, Tjian R, Rubin G. The activities of two Ets-related transcription factors required for Drosophila eye development are modulated by the Ras/MAPK pathway. Cell. 1994;78:137-47 pubmed
    ..We demonstrate that yan can repress transcription and that this repression activity is negatively regulated by the Ras1/MAPK signal, most likely through direct phosphorylation of yan by MAPK. ..
  41. Ishimaru S, Ueda R, Hinohara Y, Ohtani M, Hanafusa H. PVR plays a critical role via JNK activation in thorax closure during Drosophila metamorphosis. EMBO J. 2004;23:3984-94 pubmed
    ..In addition, we suppose that not only Rac but also Cdc42 is activated and involved in JNK activation downstream of PVR. ..
  42. Dickson B, van der Straten A, Dominguez M, Hafen E. Mutations Modulating Raf signaling in Drosophila eye development. Genetics. 1996;142:163-71 pubmed
    The R7 fate is specified during Drosophila eye development by an inductive signal transduced intracellularly via the Raf kinase...
  43. Hou X, Goldstein E, Perrimon N. Drosophila Jun relays the Jun amino-terminal kinase signal transduction pathway to the Decapentaplegic signal transduction pathway in regulating epithelial cell sheet movement. Genes Dev. 1997;11:1728-37 pubmed
    ..In contrast to previous observations, we find that both in the embryo and during photoreceptor cell determination, DJUN is not regulated by a pathway that involves MAPK. ..
  44. Rommel C, Radziwill G, Moelling K, Hafen E. Negative regulation of Raf activity by binding of 14-3-3 to the amino terminus of Raf in vivo. Mech Dev. 1997;64:95-104 pubmed
    In the developing eye of Drosophila the protein kinase D-Raf controls the specification of the R7 photoreceptor cells. We show that overexpression of wild-type D-Raf inhibits the formation of R7 cells in a dose-dependent manner...
  45. Adachi Yamada T, Fujimura Kamada K, Nishida Y, Matsumoto K. Distortion of proximodistal information causes JNK-dependent apoptosis in Drosophila wing. Nature. 1999;400:166-9 pubmed
  46. Ambrosio L, Mahowald A, Perrimon N. Requirement of the Drosophila raf homologue for torso function. Nature. 1989;342:288-91 pubmed
    ..class, l(1)polehole (l(1)ph), which is also zygotically expressed, is the Drosophila homologue of the v-raf oncogene and encodes a potential serine-and-threonine kinase...
  47. Cela C, Llimargas M. Egfr is essential for maintaining epithelial integrity during tracheal remodelling in Drosophila. Development. 2006;133:3115-25 pubmed
    ..This finding establishes a link between a developmental pathway governing tracheal formation and cell adhesiveness. ..
  48. Melnick M, Perkins L, Lee M, Ambrosio L, Perrimon N. Developmental and molecular characterization of mutations in the Drosophila-raf serine/threonine protein kinase. Development. 1993;118:127-38 pubmed
    ..This pathway, mediated through the serine/threonine protein kinase D-raf and the protein tyrosine phosphatase corkscrew, controls the domains of expression of the transcription factors ..
  49. Takahashi F, Endo S, Kojima T, Saigo K. Regulation of cell-cell contacts in developing Drosophila eyes by Dsrc41, a new, close relative of vertebrate c-src. Genes Dev. 1996;10:1645-56 pubmed
  50. Li J, Xia F, Li W. Coactivation of STAT and Ras is required for germ cell proliferation and invasive migration in Drosophila. Dev Cell. 2003;5:787-98 pubmed
    ..A requirement for RTK in Drosophila PGC development is analogous to the mouse, in which the RTK c-kit is required, suggesting a conserved molecular mechanism governing PGC behavior in flies and mammals. ..
  51. Jiang H, Edgar B. EGFR signaling regulates the proliferation of Drosophila adult midgut progenitors. Development. 2009;136:483-93 pubmed publisher
    ..Two stronger EGFR ligands, Spitz and Keren, are expressed by the AMPs themselves and provide an additional, autocrine mitogenic stimulus to the AMPs during late larval stages. ..
  52. Pawson T, Bernstein A. Receptor tyrosine kinases: genetic evidence for their role in Drosophila and mouse development. Trends Genet. 1990;6:350-6 pubmed
  53. Snee M, Wilson W, Zhu Y, Chen S, Wilson B, Kseib C, et al. Collaborative Control of Cell Cycle Progression by the RNA Exonuclease Dis3 and Ras Is Conserved Across Species. Genetics. 2016;203:749-62 pubmed publisher
    ..Thus, reduction, but not absence, of dis3 activity can enhance cell proliferation in higher organisms. ..
  54. Radke K, Baek K, Ambrosio L. Characterization of maternal and zygotic D-raf proteins: dominant negative effects on Torso signal transduction. Genetics. 1997;145:163-71 pubmed
    ..Then to determine whether rescue of the Tor pathway is influenced by pools of nonfunctional maternal D raf. wild-type D-raf mRNA was injected into embryos that inherit maternal stores of inactive 90-kD of truncated D-raf ..
  55. Morrell P, Toleno D, Lundy K, Clegg M. Estimating the contribution of mutation, recombination and gene conversion in the generation of haplotypic diversity. Genetics. 2006;173:1705-23 pubmed publisher
    ..simulans, and Zea mays. In total, 13 of 27 loci show evidence of gene conversion. For these loci, gene conversion is estimated to contribute an average of twice as much as crossing over to total recombination...