fu

Summary

Gene Symbol: fu
Description: fused
Alias: CG6551, Dm fu, Dmel\CG6551, dFu, fu[mel], l(1)fu, fused, CG6551-PA, fu-PA
Species: fruit fly
Products:     fu

Top Publications

  1. Lum L, Zhang C, Oh S, Mann R, von Kessler D, Taipale J, et al. Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2. Mol Cell. 2003;12:1261-74 pubmed
    ..accumulation and phosphorylation of Smo at the membrane as well as phosphorylation of the cytoplasmic components Fu and Su(fu)...
  2. Ruel L, Gallet A, Raisin S, Truchi A, Staccini Lavenant L, Cervantes A, et al. Phosphorylation of the atypical kinesin Costal2 by the kinase Fused induces the partial disassembly of the Smoothened-Fused-Costal2-Cubitus interruptus complex in Hedgehog signalling. Development. 2007;134:3677-89 pubmed
    ..This residue is located in the serine/threonine kinase Fused (Fu)-binding domain and is phosphorylated as a consequence of Fu activation...
  3. Apionishev S, Katanayeva N, Marks S, Kalderon D, Tomlinson A. Drosophila Smoothened phosphorylation sites essential for Hedgehog signal transduction. Nat Cell Biol. 2005;7:86-92 pubmed
  4. Ogden S, Casso D, Ascano M, Yore M, Kornberg T, Robbins D. Smoothened regulates activator and repressor functions of Hedgehog signaling via two distinct mechanisms. J Biol Chem. 2006;281:7237-43 pubmed
    ..to the Hh signaling complex, which consists of the kinesin-related protein Costal2 (Cos2), the protein kinase Fused (Fu), and the Drosophila Gli homolog cubitus interruptus (Ci), in two distinct manners...
  5. Ascano M, Nybakken K, Sosinski J, Stegman M, Robbins D. The carboxyl-terminal domain of the protein kinase fused can function as a dominant inhibitor of hedgehog signaling. Mol Cell Biol. 2002;22:1555-66 pubmed
    ..Here, we have investigated the relationship between two components of the HSC, the serine/threonine protein kinase Fused (Fu) and the kinesin-related protein Costal2 (Cos2)...
  6. Aza Blanc P, Ramirez Weber F, Laget M, Schwartz C, Kornberg T. Proteolysis that is inhibited by hedgehog targets Cubitus interruptus protein to the nucleus and converts it to a repressor. Cell. 1997;89:1043-53 pubmed
    ..Hh inhibits proteolysis of Ci, and we suggest that this inhibition leads to the observed patterns of expression of key target genes at the compartment border. ..
  7. Zhang C, Williams E, Guo Y, Lum L, Beachy P. Extensive phosphorylation of Smoothened in Hedgehog pathway activation. Proc Natl Acad Sci U S A. 2004;101:17900-7 pubmed
    ..Our studies confirm and extend previous studies showing a positive effect for cAMP-dependent protein kinase and uncover a positive role for casein kinase 1alpha in Hh pathway activation. ..
  8. Narbonne Reveau K, Besse F, Lamour Isnard C, Busson D, Pret A. fused regulates germline cyst mitosis and differentiation during Drosophila oogenesis. Mech Dev. 2006;123:197-209 pubmed
    The fused gene encodes a serine-threonine kinase that functions as a positive regulator of Hedgehog signal transduction in Drosophila embryogenesis, wing morphogenesis, and somatic cell development during oogenesis...
  9. Wang Q, Holmgren R. The subcellular localization and activity of Drosophila cubitus interruptus are regulated at multiple levels. Development. 1999;126:5097-106 pubmed
    ..Finally, we propose that there are three levels of apparent Ci activity, corresponding to three zones along the AP axis with different sets of gene expression and different levels of Hh signaling. ..

More Information

Publications64

  1. Farzan S, Ascano M, Ogden S, Sanial M, Brigui A, Plessis A, et al. Costal2 functions as a kinesin-like protein in the hedgehog signal transduction pathway. Curr Biol. 2008;18:1215-20 pubmed publisher
    ..Combined, these results demonstrate that Cos2 motility plays an important role in its function, regulating the amounts and activity of Ci that ultimately interpret the level of Hh to which cells are exposed. ..
  2. Gallet A, Ruel L, Staccini Lavenant L, Therond P. Cholesterol modification is necessary for controlled planar long-range activity of Hedgehog in Drosophila epithelia. Development. 2006;133:407-18 pubmed
    ..We conclude that, as in vertebrates, cholesterol modification is essential for controlled long-range Hh signalling in Drosophila. ..
  3. Wang G, Amanai K, Wang B, Jiang J. Interactions with Costal2 and suppressor of fused regulate nuclear translocation and activity of cubitus interruptus. Genes Dev. 2000;14:2893-905 pubmed
    ..Here, we provide evidence that Costal2 (Cos2) and Suppressor of Fused [Su(fu)] inhibit Ci by tethering it in the cytoplasm, whereas Hh induces nuclear translocaltion of Ci through ..
  4. Ogden S, Ascano M, Stegman M, Robbins D. Regulation of Hedgehog signaling: a complex story. Biochem Pharmacol. 2004;67:805-14 pubmed
    ..The HSC consists of the Kinesin Related Protein, Costal2 (Cos2), the serine-threonine protein kinase. Fused (Fu) and Ci...
  5. Ogden S, Ascano M, Stegman M, Suber L, Hooper J, Robbins D. Identification of a functional interaction between the transmembrane protein Smoothened and the kinesin-related protein Costal2. Curr Biol. 2003;13:1998-2003 pubmed
    ..At a minimum, the HSC consists of the Kinesin-related protein Costal2 (Cos2), the protein kinase Fused (Fu), and the transcription factor Cubitus interruptus (Ci)...
  6. Ranieri N, Ruel L, Gallet A, Raisin S, Therond P. Distinct phosphorylations on kinesin costal-2 mediate differential hedgehog signaling strength. Dev Cell. 2012;22:279-94 pubmed publisher
    ..In Drosophila, associations between Smo and the Fused (Fu)/Costal-2 (Cos2)/Cubitus Interruptus (Ci) cytoplasmic complex lead to pathway activation, but it remains ..
  7. Hooper J. Smoothened translates Hedgehog levels into distinct responses. Development. 2003;130:3951-63 pubmed
    ..balance through its receptor, Patched, which acts through Smoothened and thence a regulatory complex that includes Fused, Costal, Suppressor of Fused and Cubitus interruptus...
  8. Malpel S, Claret S, Sanial M, Brigui A, Piolot T, Daviet L, et al. The last 59 amino acids of Smoothened cytoplasmic tail directly bind the protein kinase Fused and negatively regulate the Hedgehog pathway. Dev Biol. 2007;303:121-33 pubmed
    ..transduction events following SMO activation depend on cytoplasmic multimeric complexes that include the Fused (FU) protein kinase...
  9. Claret S, Sanial M, Plessis A. Evidence for a novel feedback loop in the Hedgehog pathway involving Smoothened and Fused. Curr Biol. 2007;17:1326-33 pubmed
    ..SMO interacts directly with the Ser-Thr protein kinase Fused (FU) and the kinesin-related protein Costal2 (COS2), which interact with each other and with CI in an ..
  10. Cheng S, Maier D, Hipfner D. Drosophila G-protein-coupled receptor kinase 2 regulates cAMP-dependent Hedgehog signaling. Development. 2012;139:85-94 pubmed publisher
    ..Gprk2 is important for normal cAMP regulation, and thus has an indirect effect on the activity of Pka-regulated components of the Hh pathway, including Smo itself. ..
  11. Shi Q, Li S, Jia J, Jiang J. The Hedgehog-induced Smoothened conformational switch assembles a signaling complex that activates Fused by promoting its dimerization and phosphorylation. Development. 2011;138:4219-31 pubmed publisher
    ..Here, we show that Hh-induced Smo conformational change recruits Costal2 (Cos2)/Fused (Fu) and promotes Fu kinase domain dimerization...
  12. Therond P, Alves G, Limbourg Bouchon B, Tricoire H, Guillemet E, Brissard Zahraoui J, et al. Functional domains of fused, a serine-threonine kinase required for signaling in Drosophila. Genetics. 1996;142:1181-98 pubmed
    b>fused (fu) is a segment-polarity gene encoding a putative serine-threonine kinase. In a wild-type context, all fu mutations display the same set of phenotypes...
  13. Xia L, Jia S, Huang S, Wang H, Zhu Y, Mu Y, et al. The Fused/Smurf complex controls the fate of Drosophila germline stem cells by generating a gradient BMP response. Cell. 2010;143:978-90 pubmed publisher
    ..How this steep gradient of response to BMP signaling is formed has been unclear. Here, we show that Fused (Fu), a serine/threonine kinase that regulates Hedgehog, functions in concert with the E3 ligase Smurf to regulate ..
  14. Kalderon D. Transducing the hedgehog signal. Cell. 2000;103:371-4 pubmed
  15. Wang G, Jiang J. Multiple Cos2/Ci interactions regulate Ci subcellular localization through microtubule dependent and independent mechanisms. Dev Biol. 2004;268:493-505 pubmed
    ..In the absence of Hh, Ci155 is sequestered in the cytoplasm by forming protein complexes with Costal2 (Cos2), Fused (Fu) and Suppressor of Fused [Su(fu)]. How complex formation regulates Ci155 subcellular localization is not clear...
  16. Motzny C, Holmgren R. The Drosophila cubitus interruptus protein and its role in the wingless and hedgehog signal transduction pathways. Mech Dev. 1995;52:137-50 pubmed
    ..The distribution of the ci protein is altered in fused, hedgehog and wingless mutants suggesting cell-cell signaling may regulate ci protein levels...
  17. Zhou Q, Kalderon D. Hedgehog activates fused through phosphorylation to elicit a full spectrum of pathway responses. Dev Cell. 2011;20:802-14 pubmed publisher
    ..How Hh-induced activation of transmembrane Smoothened (Smo) proteins reverses Ci/Gli inhibition by Suppressor of Fused (SuFu) and kinesin family protein (Cos2/Kif7) binding partners is a major unanswered question...
  18. Marks S, Kalderon D. Regulation of mammalian Gli proteins by Costal 2 and PKA in Drosophila reveals Hedgehog pathway conservation. Development. 2011;138:2533-42 pubmed publisher
    ..We also show that direct PKA phosphorylation regulates the activity, rather than the proteolysis of Gli in Drosophilia, and we provide evidence for an analogous action of PKA on Ci. ..
  19. Johnson R, Scott M. New players and puzzles in the Hedgehog signaling pathway. Curr Opin Genet Dev. 1998;8:450-6 pubmed
    ..The role of Hh in carcinogenesis is underscored by the identification of mutations in several pathway components in skin and brain tumors. ..
  20. Raisin S, Ruel L, Ranieri N, Staccini Lavenant L, Thérond P. Dynamic phosphorylation of the kinesin Costal-2 in vivo reveals requirement of fused kinase activity for all levels of hedgehog signalling. Dev Biol. 2010;344:119-28 pubmed publisher
    ..cultured cells, phosphorylation of the kinesin-like Costal2 (Cos2) protein at Ser572 is triggered by the kinase fused (Fu) upon Hh pathway activation...
  21. Wang Q, Holmgren R. Nuclear import of cubitus interruptus is regulated by hedgehog via a mechanism distinct from Ci stabilization and Ci activation. Development. 2000;127:3131-9 pubmed
    ..Finally, we show that cos2 and pka, two molecules that have been characterized primarily as negative regulators of Ci activity, also have positive roles in the activation of Ci in response to Hh. ..
  22. Huangfu D, Anderson K. Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates. Development. 2006;133:3-14 pubmed
    ..For example, Smo structure and the roles of fused and Suppressor of fused have diverged...
  23. Sisson J, Ho K, Suyama K, Scott M. Costal2, a novel kinesin-related protein in the Hedgehog signaling pathway. Cell. 1997;90:235-45 pubmed
    ..The repressors include Costal2, protein kinase A, and the HH receptor Patched. Like HH, the kinase Fused and the transcription factor Cubitus interruptus (CI) act positively upon targets...
  24. Farese R, Herz J. Cholesterol metabolism and embryogenesis. Trends Genet. 1998;14:115-20 pubmed
    ..Shared aspects of these phenotypes suggest that common mechanisms underlie impaired central nervous system development associated with cholesterol deficiency. ..
  25. Smelkinson M, Zhou Q, Kalderon D. Regulation of Ci-SCFSlimb binding, Ci proteolysis, and hedgehog pathway activity by Ci phosphorylation. Dev Cell. 2007;13:481-95 pubmed
    ..We also show that when Ci proteolysis is compromised, its specific activity is limited principally by Su(fu), and not by Cos2 cytoplasmic tethering or PKA phosphorylation.
  26. Jia J, Tong C, Jiang J. Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail. Genes Dev. 2003;17:2709-20 pubmed
    ..Smo physically interacts with Costal2 (Cos2) and Fused (Fu) through its C-tail. Deletion of the Cos2/Fu-binding domain from Smo abolishes its signaling activity...
  27. Stegman M, Goetz J, Ascano M, Ogden S, Nybakken K, Robbins D. The Kinesin-related protein Costal2 associates with membranes in a Hedgehog-sensitive, Smoothened-independent manner. J Biol Chem. 2004;279:7064-71 pubmed
    ..complex (HSC)), which includes the Kinesin-related protein Costal2 (Cos2), the serine/threonine protein kinase Fused (Fu), and the transcription factor Cubitus interruptus (Ci)...
  28. Ruel L, Rodriguez R, Gallet A, Lavenant Staccini L, Therond P. Stability and association of Smoothened, Costal2 and Fused with Cubitus interruptus are regulated by Hedgehog. Nat Cell Biol. 2003;5:907-13 pubmed
    ..protein complex with at least two other proteins, the kinesin-like Costal2 (Cos2) and the serine-threonine kinase Fused (Fu). This protein complex governs the access of Ci to the nucleus...
  29. Preat T, Therond P, Limbourg Bouchon B, Pham A, Tricoire H, Busson D, et al. Segmental polarity in Drosophila melanogaster: genetic dissection of fused in a Suppressor of fused background reveals interaction with costal-2. Genetics. 1993;135:1047-62 pubmed
    b>fused (fu) is a segment polarity gene that encodes a putative serine/threonine kinase. A complete suppressor of the embryonic and adult phenotypes of fu mutants, Suppressor of fused (Su(fu)), was previously described...
  30. Hammerschmidt M, Brook A, McMahon A. The world according to hedgehog. Trends Genet. 1997;13:14-21 pubmed
    ..Here, we review recent experiments addressing the function of the various Hedgehog members during invertebrate and vertebrate development. ..
  31. Nusslein Volhard C, Wieschaus E. Mutations affecting segment number and polarity in Drosophila. Nature. 1980;287:795-801 pubmed
  32. Wicking C, Smyth I, Bale A. The hedgehog signalling pathway in tumorigenesis and development. Oncogene. 1999;18:7844-51 pubmed
  33. Lum L, Beachy P. The Hedgehog response network: sensors, switches, and routers. Science. 2004;304:1755-9 pubmed
  34. Methot N, Basler K. Suppressor of fused opposes hedgehog signal transduction by impeding nuclear accumulation of the activator form of Cubitus interruptus. Development. 2000;127:4001-10 pubmed
    ..We report that Cos2, PKA and Fused are necessary for the generation of Ci[rep], whereas the inhibition of either Cos2 or PKA activity is a ..
  35. Ohlmeyer J, Kalderon D. Hedgehog stimulates maturation of Cubitus interruptus into a labile transcriptional activator. Nature. 1998;396:749-53 pubmed
    ..However, Ci-155 is detected only in the cytoplasm, where it is associated with the protein kinase Fused (Fu), with Suppressor of Fused (Su(fu)), and with the microtubule-binding protein Costal-2...
  36. Zhang Y, Mao F, Lu Y, Wu W, Zhang L, Zhao Y. Transduction of the Hedgehog signal through the dimerization of Fused and the nuclear translocation of Cubitus interruptus. Cell Res. 2011;21:1436-51 pubmed publisher
    ..However, how Smo transduces the graded Hh signal via the Costal2 (Cos2)/Fused (Fu) complex remains poorly understood...
  37. Pham A, Therond P, Alves G, Tournier F, Busson D, Lamour Isnard C, et al. The Suppressor of fused gene encodes a novel PEST protein involved in Drosophila segment polarity establishment. Genetics. 1995;140:587-98 pubmed
    Suppressor of fused, Su(fu), was identified as a semi-dominant suppressor of the putative serine/threonine kinase encoded by the segment polarity gene fused in Drosophila melanogaster...
  38. Monnier V, Dussillol F, Alves G, Lamour Isnard C, Plessis A. Suppressor of fused links fused and Cubitus interruptus on the hedgehog signalling pathway. Curr Biol. 1998;8:583-6 pubmed
    ..In Drosophila, the transcription of Hh targets requires the activation of the protein kinase Fused (Fu) and the inactivation of both Suppressor of fused (Su(fu)) and Costal-2 (Cos-2) [3]...
  39. Alves G, Limbourg Bouchon B, Tricoire H, Brissard Zahraoui J, Lamour Isnard C, Busson D. Modulation of Hedgehog target gene expression by the Fused serine-threonine kinase in wing imaginal discs. Mech Dev. 1998;78:17-31 pubmed
    The Fused (Fu) serine-threonine kinase and the Suppressor of fused (Su(fu)) product are part of the Hedgehog (Hh) signaling pathway both in embryos and in imaginal discs...
  40. Ascano M, Robbins D. An intramolecular association between two domains of the protein kinase Fused is necessary for Hedgehog signaling. Mol Cell Biol. 2004;24:10397-405 pubmed
    The protein kinase Fused (Fu) is an integral member of the Hedgehog (Hh) signaling pathway...
  41. Ingham P. Transducing Hedgehog: the story so far. EMBO J. 1998;17:3505-11 pubmed
    ..Elucidating the mechanisms by which Hedgehog signals are transduced will thus have widespread implications for our understanding of both normal development and disease. ..
  42. Liu Y, Cao X, Jiang J, Jia J. Fused-Costal2 protein complex regulates Hedgehog-induced Smo phosphorylation and cell-surface accumulation. Genes Dev. 2007;21:1949-63 pubmed
    ..The intracellular signaling complex containing Fused (Fu) and Costal2 (Cos2) is thought to transduce the Hh signal downstream from Smo...
  43. Aza Blanc P, Kornberg T. Ci: a complex transducer of the hedgehog signal. Trends Genet. 1999;15:458-62 pubmed
    ..Here, we highlight recent advances in the Ci story, and discuss remaining questions whose resolution promise to help explain how morphogens like Hh signal their distant targets. ..
  44. Stegman M, Vallance J, Elangovan G, Sosinski J, Cheng Y, Robbins D. Identification of a tetrameric hedgehog signaling complex. J Biol Chem. 2000;275:21809-12 pubmed
    ..Here, we show that three members of this complex, Costal2 (Cos2), Fused (Fu), and Cubitus interruptus (Ci), bind each other directly to form a trimeric complex...
  45. Zhao Y, Tong C, Jiang J. Transducing the Hedgehog signal across the plasma membrane. Fly (Austin). 2007;1:333-6 pubmed
    ..We discuss how Smo conformational change regulates the intracellular signaling complex and how Smo transduces the graded Hh signaling activities through different conformational states. ..
  46. Ogden S, Fei D, Schilling N, Ahmed Y, Hwa J, Robbins D. G protein Galphai functions immediately downstream of Smoothened in Hedgehog signalling. Nature. 2008;456:967-70 pubmed publisher
    ..an intracellular multi-protein complex containing the Kinesin related protein Costal2 (Cos2), the protein kinase Fused (Fu) and the transcription factor Cubitus interruptus (Ci)...
  47. Thérond P, Knight J, Kornberg T, Bishop J. Phosphorylation of the fused protein kinase in response to signaling from hedgehog. Proc Natl Acad Sci U S A. 1996;93:4224-8 pubmed
    ..The Drosophila gene fused (fu) encodes a serine/threonine-protein kinase that genetic experiments have implicated in signaling initiated by ..
  48. Nybakken K, Turck C, Robbins D, Bishop J. Hedgehog-stimulated phosphorylation of the kinesin-related protein Costal2 is mediated by the serine/threonine kinase fused. J Biol Chem. 2002;277:24638-47 pubmed
    ..Within the cell, Hh signal transduction utilizes a large protein complex consisting of the Fused (Fu), Costal2 (Cos2), and Cubitis interruptus (Ci) proteins, but the functional interactions between these ..
  49. Robbins D, Nybakken K, Kobayashi R, Sisson J, Bishop J, Thérond P. Hedgehog elicits signal transduction by means of a large complex containing the kinesin-related protein costal2. Cell. 1997;90:225-34 pubmed
    ..The complex includes the products of at least three genes: fused (a protein-serine/threonine kinase), cubitus interruptus (a transcription factor), and costal2 (a kinesin-like ..
  50. Zhang W, Zhao Y, Tong C, Wang G, Wang B, Jia J, et al. Hedgehog-regulated Costal2-kinase complexes control phosphorylation and proteolytic processing of Cubitus interruptus. Dev Cell. 2005;8:267-78 pubmed
    ..We propose that Cos2 recruits multiple kinases to efficiently phosphorylate Ci and that Hh inhibits Ci phosphorylation by specifically interfering with kinase recruitment. ..
  51. Forbes A, Nakano Y, Taylor A, Ingham P. Genetic analysis of hedgehog signalling in the Drosophila embryo. Dev Suppl. 1993;:115-24 pubmed
    ..transduction of the hh-encoded signal is mediated by the activity of four other segment polarity genes, patched, fused, costal-2 and cubitus interruptus...
  52. Ingham P. Segment polarity genes and cell patterning within the Drosophila body segment. Curr Opin Genet Dev. 1991;1:261-7 pubmed
  53. Friggi Grelin F, Lavenant Staccini L, Therond P. Control of antagonistic components of the hedgehog signaling pathway by microRNAs in Drosophila. Genetics. 2008;179:429-39 pubmed publisher
    ..regulatory proteins, including the coreceptor Smoothened (Smo), the kinesin-like Costal-2 (Cos2), and the kinase Fused (Fu), is affected by Hh signaling activation...
  54. Blanchet Tournier M, Tricoire H, Busson D, Lamour Isnard C. The segment-polarity gene fused is highly conserved in Drosophila. Gene. 1995;161:157-62 pubmed
    The segment polarity gene fused (fu) is involved in specification of positional information inside embryonic segments in Drosophila melanogaster (Dm)...
  55. DiNardo S, Sher E, Heemskerk Jongens J, Kassis J, O Farrell P. Two-tiered regulation of spatially patterned engrailed gene expression during Drosophila embryogenesis. Nature. 1988;332:604-9 pubmed
    ..This late programme maintains and perhaps modifies the striped pattern of engrailed expression through interactions that may involve cell communication. ..