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Gene Review

R  -  Roughened

Drosophila melanogaster

Synonyms: BEST:GH18528, C-ras3, CG1956, D-Rap1, DRap, ...
 
 
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Disease relevance of R

 

High impact information on R

  • Drosophila Rap1 protein is 88% identical to human rap1A/K-rev1 protein, a putative antagonist of ras action [2].
  • The Roughened mutation disrupts the early stages of photoreceptor cell determination [2].
  • Mutations at the Darkener of apricot (Doa) locus of Drosophila cause roughened eyes and increase transcript accumulation from the retrotransposon copia up to fourfold [3].
  • Our experiments show that Rap1 is not needed for cell proliferation and cell-fate specification but demonstrate a critical function for Rap1 in regulating normal morphogenesis in the eye disk, the ovary and the embryo [4].
  • More recent experiments indicate functions in calcium- and cAMP-mediated signaling and it has been proposed that protein kinase A-mediated phosphorylation activates Rap in vivo [4].
 

Biological context of R

 

Anatomical context of R

  • Cno binds to the activated form of Rap1 in a yeast two-hybrid assay, the two molecules colocalize to the adherens junction, and they display very similar phenotypes in embryonic dorsal closure (DC), a process that relies on the elongation and migration of epithelial cell sheets [8].
  • They reveal a signaling circuitry where Ral is functionally downstream of the Rap GTPase, at odds with the pathways described for mammalian cell lines [9].
  • The PDZ-GEF dizzy regulates cell shape of migrating macrophages via Rap1 and integrins in the Drosophila embryo [10].
  • Thus, the Rap signaling/E-cadherin pathway may represent one mechanism that regulates polarized niche formation and stem cell anchoring [11].
 

Associations of R with chemical compounds

 

Physical interactions of R

  • We show that D-Rap1 binds D-Raf and activates ERKs in a GTP- and D-Raf-dependent manner [5].
 

Other interactions of R

  • Here, we present biochemical and genetic evidence that D-Rap1, the Drosophila homolog of Rap1, can activate D-Raf and ERK [5].
  • Genetic interaction experiments show that Rap1 and Cno act in the same molecular pathway during DC and that the function of both molecules in DC depends on their ability to interact [8].
  • Interestingly, overexpression of Rap/Fzr in the eye primordia also increases the size of the antennal primordium resulting in the induction of ectopic antennae [6].
  • Our results show that, in addition to constitutive transcripts, the src, abl, ras1 and ras3 genes express a set of maternal/embryonic-specific transcripts [15].

References

  1. Biological characterization of Drosophila Rapgap1, a GTPase activating protein for Rap1. Chen, F., Barkett, M., Ram, K.T., Quintanilla, A., Hariharan, I.K. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  2. The Drosophila roughened mutation: activation of a rap homolog disrupts eye development and interferes with cell determination. Hariharan, I.K., Carthew, R.W., Rubin, G.M. Cell (1991) [Pubmed]
  3. The Doa locus encodes a member of a new protein kinase family and is essential for eye and embryonic development in Drosophila melanogaster. Yun, B., Farkas, R., Lee, K., Rabinow, L. Genes Dev. (1994) [Pubmed]
  4. The Rap1 GTPase functions as a regulator of morphogenesis in vivo. Asha, H., de Ruiter, N.D., Wang, M.G., Hariharan, I.K. EMBO J. (1999) [Pubmed]
  5. 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]
  6. rap gene encodes Fizzy-related protein (Fzr) and regulates cell proliferation and pattern formation in the developing Drosophila eye-antennal disc. Pimentel, A.C., Venkatesh, T.R. Dev. Biol. (2005) [Pubmed]
  7. The genetics of the Dras3-Roughened-ecdysoneless chromosomal region (62B3-4 to 62D3-4) in Drosophila melanogaster: analysis of recessive lethal mutations. Sliter, T.J., Henrich, V.C., Tucker, R.L., Gilbert, L.I. Genetics (1989) [Pubmed]
  8. The AF-6 homolog canoe acts as a Rap1 effector during dorsal closure of the Drosophila embryo. Boettner, B., Harjes, P., Ishimaru, S., Heke, M., Fan, H.Q., Qin, Y., Van Aelst, L., Gaul, U. Genetics (2003) [Pubmed]
  9. A Ral guanine exchange factor-Ral pathway is conserved in Drosophila melanogaster and sheds new light on the connectivity of the Ral, Ras, and Rap pathways. Mirey, G., Balakireva, M., L'Hoste, S., Rossé, C., Voegeling, S., Camonis, J. Mol. Cell. Biol. (2003) [Pubmed]
  10. The PDZ-GEF dizzy regulates cell shape of migrating macrophages via Rap1 and integrins in the Drosophila embryo. Huelsmann, S., Hepper, C., Marchese, D., Knöll, C., Reuter, R. Development (2006) [Pubmed]
  11. Rap-GEF signaling controls stem cell anchoring to their niche through regulating DE-cadherin-mediated cell adhesion in the Drosophila testis. Wang, H., Singh, S.R., Zheng, Z., Oh, S.W., Chen, X., Edwards, K., Hou, S.X. Dev. Cell (2006) [Pubmed]
  12. Rap1 GTPase regulation of adherens junction positioning and cell adhesion. Knox, A.L., Brown, N.H. Science (2002) [Pubmed]
  13. Drosophila PDZ-GEF, a guanine nucleotide exchange factor for Rap1 GTPase, reveals a novel upstream regulatory mechanism in the mitogen-activated protein kinase signaling pathway. Lee, J.H., Cho, K.S., Lee, J., Kim, D., Lee, S.B., Yoo, J., Cha, G.H., Chung, J. Mol. Cell. Biol. (2002) [Pubmed]
  14. Human cDNAs rap1 and rap2 homologous to the Drosophila gene Dras3 encode proteins closely related to ras in the 'effector' region. Pizon, V., Chardin, P., Lerosey, I., Olofsson, B., Tavitian, A. Oncogene (1988) [Pubmed]
  15. Maternal and embryonic transcripts of Drosophila proto-oncogenes are expressed in Schneider 2 culture cells but not in l(2)gl transformed neuroblasts. Kimchie, Z., Segev, O., Lev, Z. Cell Differ. Dev. (1989) [Pubmed]
 
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