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Gene Review

phl  -  pole hole

Drosophila melanogaster

Synonyms: 11-29, C110, CG2845, D-RAF, D-Raf, ...
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High impact information on phl


Biological context of phl


Anatomical context of phl

  • We also characterize the accumulation of maternal D-raf proteins in 0-2-hr embryos derived from females with germ cells lacking D-raf activity [8].
  • We also find that mKSR1 associates with Raf-1 at the plasma membrane in a Ras-dependent manner, indicating the presence of a membrane-bound kinase signaling complex [9].
  • Here we identify a novel family of Drosophila proteins, Nasrat and Polehole, that coat the oocyte surface and play two roles: They mediate assembly of the eggshell, and act in the Torso RTK signaling pathway that specifies the terminal regions of the embryo [10].
  • Thus, we provide evidence that zygotic D-raf acts to specify cell fates in two distinct pathways that generate dorsoventral pattern within the ectoderm [11].
  • However, in contrast to the dominant active mutant of Ki-Ras, which interacts with Raf-1, recruits it to the plasma membrane from the cytosol, and activates it, MAGUIN-1 neither activates Raf-1 nor recruits it to the plasma membrane [12].

Associations of phl with chemical compounds

  • The D-raf gene product, which is required for Torso function, is identified as a 90-kDa protein with intrinsic serine/threonine kinase activity [6].
  • Membrane-targeted D-raftor4021 showed the highest level of activity, followed by alanine-substituted D-rafS388A and N-terminal-truncated D-raf delta 445 [13].
  • Association of membrane-associated guanylate kinase-interacting protein-1 with Raf-1 [12].

Physical interactions of phl

  • We show that D-Rap1 binds D-Raf and activates ERKs in a GTP- and D-Raf-dependent manner [7].
  • We also found that the D-STAT-binding site is required for injury-induced activation of the D-raf gene promoter [14].
  • These findings suggest that mutant forms of D-raf may deplete the embryo of a positive activator and/or form inactive protein complexes that affect rescue of the Tor pathway [8].
  • Cell surface proteins Nasrat and Polehole stabilize the Torso-like extracellular determinant in Drosophila oogenesis [10].

Regulatory relationships of phl

  • Eight alleles of Dsor1 encoding a Drosophila homologue of mitogen-activated protein (MAP) kinase kinase were obtained as dominant suppressors of the MAP kinase kinase kinase D raf [15].
  • Here we propose that D-STAT can participate in regulation of the mitogen-activated protein kinase cascade through D-raf gene activation [14].
  • Unexpectedly, we also report that the C-terminal region of CNK contains a short bipartite element that strongly inhibits RAF catalytic function [16].
  • Furthermore, half reduction of the D-raf gene dose suppressed this DREF-induced vein of increased width phenotype [17].

Other interactions of phl

  • Here, we demonstrate that Hop requires the activity of the Raf pathway to promote the activation response of larval plasmatocytes, and provide evidence to suggest that the Hop and D-Raf proteins physically interact [18].
  • Here, we present biochemical and genetic evidence that D-Rap1, the Drosophila homolog of Rap1, can activate D-Raf and ERK [7].
  • This signaling pathway is mediated by the serine/threonine kinase D-raf and a protein tyrosine phosphatase corkscrew (csw) [19].
  • The Drosophila raf (D-raf) gene promoter contains a recognition consensus sequence for Drosophila STAT (D-STAT) [14].
  • By analogy to catalytically impaired, but conformationally active B-RAF oncogenic mutants, we discuss the possibility that KSR represents a natural allosteric inducer of RAF catalytic function [20].

Analytical, diagnostic and therapeutic context of phl

  • As assessed by DNase I footprinting and promoter dissection experiments, two of these elements are potential regulatory targets of Raf-1-activated transcription factors [21].
  • The most closely related to v-raf was mapped by in situ hybridization to position 2F5-6 (Draf-1) on the X chromosome, whereas the other raf-related gene (Draf-2) was found at position 43A2-5 on chromosome 2 [22].
  • We demonstrate, using a series of mutations in the signal transducers Corkscrew/SHP-2 and D-Raf, that quantitative variations in the magnitude of MAPK activity trigger both qualitatively and quantitatively distinct transcriptional responses [23].


  1. The torso receptor tyrosine kinase can activate Raf in a Ras-independent pathway. Hou, X.S., Chou, T.B., Melnick, M.B., Perrimon, N. Cell (1995) [Pubmed]
  2. A protein kinase similar to MAP kinase activator acts downstream of the raf kinase in Drosophila. Tsuda, L., Inoue, Y.H., Yoo, M.A., Mizuno, M., Hata, M., Lim, Y.M., Adachi-Yamada, T., Ryo, H., Masamune, Y., Nishida, Y. Cell (1993) [Pubmed]
  3. Down-regulation of the Drosophila morphogen bicoid by the torso receptor-mediated signal transduction cascade. Ronchi, E., Treisman, J., Dostatni, N., Struhl, G., Desplan, C. Cell (1993) [Pubmed]
  4. Requirement of the Drosophila raf homologue for torso function. Ambrosio, L., Mahowald, A.P., Perrimon, N. Nature (1989) [Pubmed]
  5. Src42 binding activity regulates Drosophila RAF by a novel CNK-dependent derepression mechanism. Laberge, G., Douziech, M., Therrien, M. EMBO J. (2005) [Pubmed]
  6. Biochemical analysis of torso and D-raf during Drosophila embryogenesis: implications for terminal signal transduction. Sprenger, F., Trosclair, M.M., Morrison, D.K. Mol. Cell. Biol. (1993) [Pubmed]
  7. Ras-independent activation of ERK signaling via the torso receptor tyrosine kinase is mediated by Rap1. Mishra, S., Smolik, S.M., Forte, M.A., Stork, P.J. Curr. Biol. (2005) [Pubmed]
  8. Characterization of maternal and zygotic D-raf proteins: dominant negative effects on Torso signal transduction. Radke, K., Baek, K.H., Ambrosio, L. Genetics (1997) [Pubmed]
  9. KSR modulates signal propagation within the MAPK cascade. Therrien, M., Michaud, N.R., Rubin, G.M., Morrison, D.K. Genes Dev. (1996) [Pubmed]
  10. Cell surface proteins Nasrat and Polehole stabilize the Torso-like extracellular determinant in Drosophila oogenesis. Jiménez, G., González-Reyes, A., Casanova, J. Genes Dev. (2002) [Pubmed]
  11. Drosophila-raf acts to elaborate dorsoventral pattern in the ectoderm of developing embryos. Radke, K., Johnson, K., Guo, R., Davidson, A., Ambrosio, L. Genetics (2001) [Pubmed]
  12. Association of membrane-associated guanylate kinase-interacting protein-1 with Raf-1. Yao, I., Ohtsuka, T., Kawabe, H., Matsuura, Y., Takai, Y., Hata, Y. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  13. The activity of D-raf in torso signal transduction is altered by serine substitution, N-terminal deletion, and membrane targeting. Baek, K.H., Fabian, J.R., Sprenger, F., Morrison, D.K., Ambrosio, L. Dev. Biol. (1996) [Pubmed]
  14. Transcriptional regulation of the Drosophila raf proto-oncogene by Drosophila STAT during development and in immune response. Kwon, E.J., Park, H.S., Kim, Y.S., Oh, E.J., Nishida, Y., Matsukage, A., Yoo, M.A., Yamaguchi, M. J. Biol. Chem. (2000) [Pubmed]
  15. Dominant mutations of Drosophila MAP kinase kinase and their activities in Drosophila and yeast MAP kinase cascades. Lim, Y.M., Tsuda, L., Inoue, Y.H., Irie, K., Adachi-Yamada, T., Hata, M., Nishi, Y., Matsumoto, K., Nishida, Y. Genetics (1997) [Pubmed]
  16. Bimodal regulation of RAF by CNK in Drosophila. Douziech, M., Roy, F., Laberge, G., Lefrançois, M., Armengod, A.V., Therrien, M. EMBO J. (2003) [Pubmed]
  17. DREF is required for EGFR signalling during Drosophila wing vein development. Yoshida, H., Kwon, E., Hirose, F., Otsuki, K., Yamada, M., Yamaguchi, M. Genes Cells (2004) [Pubmed]
  18. The Hopscotch Jak kinase requires the Raf pathway to promote blood cell activation and differentiation in Drosophila. Luo, H., Rose, P.E., Roberts, T.M., Dearolf, C.R. Mol. Genet. Genomics (2002) [Pubmed]
  19. Control of cell fate determination by p21ras/Ras1, an essential component of torso signaling in Drosophila. Lu, X., Chou, T.B., Williams, N.G., Roberts, T., Perrimon, N. Genes Dev. (1993) [Pubmed]
  20. A KSR/CNK complex mediated by HYP, a novel SAM domain-containing protein, regulates RAS-dependent RAF activation in Drosophila. Douziech, M., Sahmi, M., Laberge, G., Therrien, M. Genes Dev. (2006) [Pubmed]
  21. Characterization of downstream elements in a Raf-1 pathway. Liaw, G.J., Steingrimsson, E., Pignoni, F., Courey, A.J., Lengyel, J.A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  22. Drosophila melanogaster homologs of the raf oncogene. Mark, G.E., MacIntyre, R.J., Digan, M.E., Ambrosio, L., Perrimon, N. Mol. Cell. Biol. (1987) [Pubmed]
  23. Quantitative variations in the level of MAPK activity control patterning of the embryonic termini in Drosophila. Ghiglione, C., Perrimon, N., Perkins, L.A. Dev. Biol. (1999) [Pubmed]
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