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Gene Review

Dsor1  -  Downstream of raf1

Drosophila melanogaster

Synonyms: CG15793, D-MEK, D-MEK/Dsor, D-Mek, D-SOR, ...
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High impact information on Dsor1

  • Dsor1Su1 mapped on X chromosome significantly suppressed the D-raf mutant phenotypes, and the loss-of-function mutations of Dsor1 showed phenotypes similar to those of the D-raf null mutations [1].
  • Sequential activation of the intermediates in the Ras/Raf serine-threonine protein kinase/MAPK kinase/MAPK/transcription factor pathway has emerged as a central mechanism for controlling cell proliferation and differentiation in yeast, worms, fruitflies and mammals [2].
  • Here, we show that KSR functions upstream of MEK within the ERK/MAPK module [3].
  • In this report, we demonstrate that CF2 is the target of down-regulation by the MAPK kinase cascade, and that this down-regulation is independent of the Rho function [4].
  • Ras1 and downstream cytoplasmic kinases, Raf, MEK, and MAPK, comprise an evolutionarily conserved cascade that mediates the transmission of signals from RTKs at the plasma membrane to specific factors in the nucleus [5].

Biological context of Dsor1

  • This portion of the pathway is likely to act as a control point in signal transduction, because the more downstream components Dsor1, corkscrew and Ksr, each show several amino acid replacements between the species [6].
  • The expression of an activated from of Dsor1 in each of the mutants effectively induced a normal, functional vulva, that is, suppressed the vulvaless phenotype [7].
  • In agreement with this, we found that KSR facilitates the phosphorylation of MEK by RAF [3].
  • Loss-of-function mutations in the genes encoding RAF, MEK, MAPK and KSR dominantly suppress RAS1V12-induced cell proliferation [8].
  • Conversely, cell death induced by overexpression of Hid was suppressed by gain-of-function mutations of the genes coding for MEK and ERK [9].

Anatomical context of Dsor1

  • The discovery of a second MAPK kinase in Drosophila provides new insights into mechanisms that control the coordinated movement of epithelial cells [10].

Associations of Dsor1 with chemical compounds

  • A temperature-sensitive MEK mutation demonstrates the conservation of the signaling pathways activated by receptor tyrosine kinases [11].

Regulatory relationships of Dsor1

  • 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 [12].

Other interactions of Dsor1

  • Furthermore, the Dsor1 alleles showed no significant interaction with gain-of-function mutations of DER [12].
  • We also demonstrate that Dsor1, which has been placed upstream of rl genetically, is able to phosphorylate and activate Rl in vitro [13].
  • MEK, a dual specificity threonine/tyrosine kinase, has been postulated to be a convergent point for signaling from receptor protein tyrosine kinases (RTKs) and G-protein-coupled receptors [11].
  • Mutations in the Drosophila homologues of Raf, MEK, MAPK, type I Geranylgeranyl Transferase and Protein Phosphatase 2A were isolated, as were mutations in several novel signaling genes [14].

Analytical, diagnostic and therapeutic context of Dsor1

  • Molecular cloning of Dsor1 revealed its product with striking similarity to the microtubule-associated protein (MAP) kinase activator and yeast PBS2, STE7, and byr1 [1].


  1. 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]
  2. Mediation of PACAP-like neuropeptide transmission by coactivation of Ras/Raf and cAMP signal transduction pathways in Drosophila. Zhong, Y. Nature (1995) [Pubmed]
  3. KSR is a scaffold required for activation of the ERK/MAPK module. Roy, F., Laberge, G., Douziech, M., Ferland-McCollough, D., Therrien, M. Genes Dev. (2002) [Pubmed]
  4. Down-regulation of transcription factor CF2 by Drosophila Ras/MAP kinase signaling in oogenesis: cytoplasmic retention and degradation. Mantrova, E.Y., Hsu, T. Genes Dev. (1998) [Pubmed]
  5. Protein phosphatase 2A positively and negatively regulates Ras1-mediated photoreceptor development in Drosophila. Wassarman, D.A., Solomon, N.M., Chang, H.C., Karim, F.D., Therrien, M., Rubin, G.M. Genes Dev. (1996) [Pubmed]
  6. Contrasting selection pressures on components of the Ras-mediated signal transduction pathway in Drosophila. Riley, R.M., Jin, W., Gibson, G. Mol. Ecol. (2003) [Pubmed]
  7. Drosophila MAP kinase kinase suppresses the vulvaless phenotype of lin-3, let-23 and lin-45 mutations in Caenorhabditis elegans. Koga, M., Ohshima, Y. Mech. Dev. (1995) [Pubmed]
  8. Ectopic expression of activated Ras1 induces hyperplastic growth and increased cell death in Drosophila imaginal tissues. Karim, F.D., Rubin, G.M. Development (1998) [Pubmed]
  9. Argos induces programmed cell death in the developing Drosophila eye by inhibition of the Ras pathway. Sawamoto, K., Taguchi, A., Hirota, Y., Yamada, C., Jin, M.H., Okano, H. Cell Death Differ. (1998) [Pubmed]
  10. Drosophila morphogenesis: follow-my-leader in epithelia. Knust, E. Curr. Biol. (1996) [Pubmed]
  11. A temperature-sensitive MEK mutation demonstrates the conservation of the signaling pathways activated by receptor tyrosine kinases. Hsu, J.C., Perrimon, N. Genes Dev. (1994) [Pubmed]
  12. 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]
  13. Biochemical characterization of rolledSem, an activated form of Drosophila mitogen-activated protein kinase. Oellers, N., Hafen, E. J. Biol. Chem. (1996) [Pubmed]
  14. A screen for genes that function downstream of Ras1 during Drosophila eye development. Karim, F.D., Chang, H.C., Therrien, M., Wassarman, D.A., Laverty, T., Rubin, G.M. Genetics (1996) [Pubmed]
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