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Gene Review

fu  -  fused

Drosophila melanogaster

Synonyms: CG6551, Dm fu, Dmel\CG6551, FU, Fu, ...
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Disease relevance of fu


High impact information on fu

  • Conversely, eliminating Fu kinase activity reduces Hh-target gene expression while increasing Ci-155 concentration [2].
  • Deletion of the Cos2/Fu-binding domain from Smo abolishes its signaling activity [3].
  • The Fused kinase has been demonstrated to phosphorylate the kinesin-like protein Costal2 and the sites identified, while Cubitus interruptus has been shown to be phosphorylated in a hierarchical manner by three different kinases [4].
  • The Drosophila gene fused (fu) encodes a serine/threonine-protein kinase that genetic experiments have implicated in signaling initiated by hedgehog [5].
  • We demonstrate that DeltaFu colocalizes with Cos2 in the presence of Fu-tail and that this colocalization occurs on a subset of membrane vesicles previously characterized to be important for Hh signal transduction [6].

Chemical compound and disease context of fu


Biological context of fu

  • This model is consistent with genetic data demonstrating that Su(fu) is not required for Hh signal transduction proper and with the elaborate genetic interactions observed among Su(fu), fu, cos2, and ci [7].
  • We also show that the Su(fu) protein is poly-phosphorylated during embryonic development and these phosphorylation events are altered in fu mutants [8].
  • Our results support the idea that Hh controls target gene expression in a concentration-dependent manner and highlight the importance of the Fu kinase in this differential regulation [9].
  • These flies exhibit a phenotype similar to that seen in fu mutants and consistent with an hh loss-of-function phenotype [10].
  • Addition of Su(fu) to the core complex blocks nuclear import while the addition of Fu restores Hh regulation of Ci nuclear import and proteolytic cleavage [11].

Associations of fu with chemical compounds

  • fused (fu) is a segment polarity gene that encodes a putative serine/threonine kinase [12].
  • Furthermore, mutational analyses of threonine 158 and serine 159, in the activation segment of the Fu protein kinase, indicate that threonine 158 is essential for Fu activity and that phosphorylation of this threonine residue may be involved in the activation of the kinase catalytic activity upon Hh stimulation [13].
  • Mutation of serine 572 to alanine eliminates most, but not all, specific phosphopeptides of Cos2 when coexpressed with Fu [1].
  • Inhibition of Hsp90 function by geldanamycin (GA) induces rapid degradation of Fu through a ubiquitin-proteasome pathway [14].
  • Two ethyl methanesulfonate mutageneses were carried out in order to isolate suppressors of the fu phenotype [15].

Physical interactions of fu

  • In these cells, Fu may be involved in the stabilization of a large protein complex which is probably responsible for the regulation of Ci cleavage and/or targeting to nucleus [16].
  • We conclude that the carboxyl-terminal domain of Fu can function in a dominant negative manner, by preventing endogenous Fu from binding to Cos2 [10].

Regulatory relationships of fu

  • These effects were all enhanced in a fu mutant context and were suppressed by cubitus interruptus (Ci) overexpression [8].
  • The fu gene discriminates between pathways to control dpp expression in Drosophila imaginal discs [17].

Other interactions of fu

  • Modulation of Hedgehog target gene expression by the Fused serine-threonine kinase in wing imaginal discs [16].
  • Here we show that, consequent on the stabilization of Smo, Cos2 and Fu are destabilized [18].
  • The expression pattern of wingless and engrailed in fu and fu;Su(fu) embryos is in accordance with this interpretation [12].
  • Evidence that oro function is involved in Hh signal transduction during embryogenesis is provided by its genetic interactions with the segment polarity genes patched (ptc) and fused (fu) [19].
  • However, unlike fu, strong kn mutations do not affect embryonic segmentation and indicate that kn is not a component of a general Hh (Hedgehog)-signaling pathway [20].

Analytical, diagnostic and therapeutic context of fu

  • We have used this suppressor as a tool to perform a genetic dissection of the fu gene [12].
  • Using the yeast two-hybrid method and an in vitro binding assay, we show that Su(fu), Ci and Fu can interact directly to form a trimolecular complex, with Su(fu) binding to both its partners simultaneously [21].


  1. Hedgehog-stimulated phosphorylation of the kinesin-related protein Costal2 is mediated by the serine/threonine kinase fused. Nybakken, K.E., Turck, C.W., Robbins, D.J., Bishop, J.M. J. Biol. Chem. (2002) [Pubmed]
  2. Hedgehog stimulates maturation of Cubitus interruptus into a labile transcriptional activator. Ohlmeyer, J.T., Kalderon, D. Nature (1998) [Pubmed]
  3. Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail. Jia, J., Tong, C., Jiang, J. Genes Dev. (2003) [Pubmed]
  4. Hedgehog signal transduction: recent findings. Nybakken, K., Perrimon, N. Curr. Opin. Genet. Dev. (2002) [Pubmed]
  5. Phosphorylation of the fused protein kinase in response to signaling from hedgehog. Thérond, P.P., Knight, J.D., Kornberg, T.B., Bishop, J.M. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  6. An intramolecular association between two domains of the protein kinase Fused is necessary for Hedgehog signaling. Ascano, M., Robbins, D.J. Mol. Cell. Biol. (2004) [Pubmed]
  7. Identification of a tetrameric hedgehog signaling complex. Stegman, M.A., Vallance, J.E., Elangovan, G., Sosinski, J., Cheng, Y., Robbins, D.J. J. Biol. Chem. (2000) [Pubmed]
  8. Modulation of the Suppressor of fused protein regulates the Hedgehog signaling pathway in Drosophila embryo and imaginal discs. Dussillol-Godar, F., Brissard-Zahraoui, J., Limbourg-Bouchon, B., Boucher, D., Fouix, S., Lamour-Isnard, C., Plessis, A., Busson, D. Dev. Biol. (2006) [Pubmed]
  9. The COE transcription factor Collier is a mediator of short-range Hedgehog-induced patterning of the Drosophila wing. Vervoort, M., Crozatier, M., Valle, D., Vincent, A. Curr. Biol. (1999) [Pubmed]
  10. The carboxyl-terminal domain of the protein kinase fused can function as a dominant inhibitor of hedgehog signaling. Ascano, M., Nybakken, K.E., Sosinski, J., Stegman, M.A., Robbins, D.J. Mol. Cell. Biol. (2002) [Pubmed]
  11. Genetic dissection of the Drosophila Cubitus interruptus signaling complex. Lefers, M.A., Wang, Q.T., Holmgren, R.A. Dev. Biol. (2001) [Pubmed]
  12. Segmental polarity in Drosophila melanogaster: genetic dissection of fused in a Suppressor of fused background reveals interaction with costal-2. Préat, T., Thérond, P., Limbourg-Bouchon, B., Pham, A., Tricoire, H., Busson, D., Lamour-Isnard, C. Genetics (1993) [Pubmed]
  13. The fused protein kinase regulates Hedgehog-stimulated transcriptional activation in Drosophila Schneider 2 cells. Fukumoto, T., Watanabe-Fukunaga, R., Fujisawa, K., Nagata, S., Fukunaga, R. J. Biol. Chem. (2001) [Pubmed]
  14. Fused kinase is stabilized by Cdc37/Hsp90 and enhances Gli protein levels. Kise, Y., Takenaka, K., Tezuka, T., Yamamoto, T., Miki, H. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  15. Characterization of Suppressor of fused, a complete suppressor of the fused segment polarity gene of Drosophila melanogaster. Préat, T. Genetics (1992) [Pubmed]
  16. Modulation of Hedgehog target gene expression by the Fused serine-threonine kinase in wing imaginal discs. Alves, G., Limbourg-Bouchon, B., Tricoire, H., Brissard-Zahraoui, J., Lamour-Isnard, C., Busson, D. Mech. Dev. (1998) [Pubmed]
  17. The fu gene discriminates between pathways to control dpp expression in Drosophila imaginal discs. Sánchez-Herrero, E., Couso, J.P., Capdevila, J., Guerrero, I. Mech. Dev. (1996) [Pubmed]
  18. Stability and association of Smoothened, Costal2 and Fused with Cubitus interruptus are regulated by Hedgehog. Ruel, L., Rodriguez, R., Gallet, A., Lavenant-Staccini, L., Thérond, P.P. Nat. Cell Biol. (2003) [Pubmed]
  19. oroshigane, a new segment polarity gene of Drosophila melanogaster, functions in hedgehog signal transduction. Epps, J.L., Jones, J.B., Tanda, S. Genetics (1997) [Pubmed]
  20. Role of knot (kn) in wing patterning in Drosophila. Nestoras, K., Lee, H., Mohler, J. Genetics (1997) [Pubmed]
  21. Suppressor of fused links fused and Cubitus interruptus on the hedgehog signalling pathway. Monnier, V., Dussillol, F., Alves, G., Lamour-Isnard, C., Plessis, A. Curr. Biol. (1998) [Pubmed]
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