Gene Symbol: cos
Description: costa
Alias: CG1708, COS2, COS[2], Cos, Cos-2, Cos2, Cos[2], DmCos2, Dmel\CG1708, KIF26A/B, Kif7, cos-2, cos2, l(2)161/28, l(2)cos[[2]], l(2)k16101, l(2)k16128, costa, CG1708-PA, CG1708-PB, Costal-2, Costal2, DmCostal2, Kinesin_B, cos-PA, cos-PB, costal 2, enhancer of epaulette
Species: fruit fly
Products:     cos

Top Publications

  1. 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
    ..These results, together with previous genetic and molecular data, suggest that fused and Suppressor of fused could act through a competitive posttraductionnal modification of a common target in the hedgehog signaling pathway. ..
  2. Kalderon D. Transducing the hedgehog signal. Cell. 2000;103:371-4 pubmed
  3. 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. ..
  4. 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. ..
  5. 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 intracellular Hedgehog transducing complex [7-9]...
  6. 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
    ..In this study, we analyse the regulation of the kinesin-like protein Costal2 (Cos2) by Hh...
  7. Wang Y, Price M. A unique protection signal in Cubitus interruptus prevents its complete proteasomal degradation. Mol Cell Biol. 2008;28:5555-68 pubmed publisher
    ..We present a model whereby the zinc finger region and K750 together form a unique protection signal that prevents the complete degradation of Ci by the proteasome. ..
  8. 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
    ..Although Costal2 (Cos2) is a requisite component of the Hh pathway, its mechanistic role is not well understood...
  9. Capdevila J, Guerrero I. Targeted expression of the signaling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings. EMBO J. 1994;13:4459-68 pubmed

More Information


  1. 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. ..
  2. 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
    ..In Drosophila cultured cells, phosphorylation of the kinesin-like Costal2 (Cos2) protein at Ser572 is triggered by the kinase fused (Fu) upon Hh pathway activation...
  3. 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...
  4. 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 ..
  5. Jia H, Liu Y, Yan W, Jia J. PP4 and PP2A regulate Hedgehog signaling by controlling Smo and Ci phosphorylation. Development. 2009;136:307-16 pubmed publisher
    ..Mechanistically, we show that Hh downregulates Smo-PP4 interaction that is mediated by Cos2. We also provide evidence that PP2A is a Ci phosphatase...
  6. Zhu A, Zheng L, Suyama K, Scott M. Altered localization of Drosophila Smoothened protein activates Hedgehog signal transduction. Genes Dev. 2003;17:1240-52 pubmed
    ..Ptc and the kinesin-related protein Costal2 (Cos2) cause internalization of Smo, a process that is dependent on both actin and microtubules...
  7. Wicking C, Smyth I, Bale A. The hedgehog signalling pathway in tumorigenesis and development. Oncogene. 1999;18:7844-51 pubmed
  8. 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. ..
  9. 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
    ..These include intra-flagellar transport proteins, which link vertebrate Hh signaling to cilia. Because abnormal Hh signaling can cause birth defects and cancer, these vertebrate-specific components may have roles in human health. ..
  10. 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 require a multiprotein complex (Hedgehog signaling complex (HSC)), which includes the Kinesin-related protein Costal2 (Cos2), the serine/threonine protein kinase Fused (Fu), and the transcription factor Cubitus interruptus (Ci)...
  11. 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...
  12. 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...
  13. Varjosalo M, Li S, Taipale J. Divergence of hedgehog signal transduction mechanism between Drosophila and mammals. Dev Cell. 2006;10:177-86 pubmed
    ..In Drosophila, the kinesin-like protein Costal2 (Cos2), which associates directly with the Hh receptor component Smoothened (Smo), is essential for suppression ..
  14. 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
    ..between two components of the HSC, the serine/threonine protein kinase Fused (Fu) and the kinesin-related protein Costal2 (Cos2)...
  15. Jia J, Amanai K, Wang G, Tang J, Wang B, Jiang J. Shaggy/GSK3 antagonizes Hedgehog signalling by regulating Cubitus interruptus. Nature. 2002;416:548-52 pubmed
    ..We propose that Sgg/GSK3 acts in conjunction with PKA to cause hyperphosphorylation of Ci, which targets it for proteolytic processing, and that Hh opposes Ci proteolysis by promoting its dephosphorylation. ..
  16. 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
    ..directly with a Ci-containing complex that is scaffolded and stabilized by the atypical kinesin, Costal-2 (Cos2)...
  17. 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
    ..Smo signals to an intracellular multi-protein complex containing the Kinesin related protein Costal2 (Cos2), the protein kinase Fused (Fu) and the transcription factor Cubitus interruptus (Ci)...
  18. 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
    ..Here, we show that these kinases physically interact with the kinesin-like protein Costal2 (Cos2) to control Ci processing and that Hh inhibits such interaction...
  19. Østerlund T, Kogerman P. Hedgehog signalling: how to get from Smo to Ci and Gli. Trends Cell Biol. 2006;16:176-80 pubmed
    ..Here, we discuss this evidence and its importance for investigations of the pathway and related biology, as well as for the development of drugs targeting components of the pathway for treatment of associated pathologies. ..
  20. 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...
  21. 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. ..
  22. Molnar C, Ruiz Gomez A, Martin M, Rojo Berciano S, Mayor F, de Celis J. Role of the Drosophila non-visual ß-arrestin kurtz in hedgehog signalling. PLoS Genet. 2011;7:e1001335 pubmed publisher
  23. 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. ..
  24. 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 ..
  25. 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 the mechanisms that regulate Ci/Gli protein activities, including the role of the kinesin-family protein Costal 2 (Cos2), which directs Ci processing in Drosophila...
  26. 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
    ..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...
  27. Chen Y, Jiang J. Decoding the phosphorylation code in Hedgehog signal transduction. Cell Res. 2013;23:186-200 pubmed publisher
    ..In this review, we focus on the multifaceted roles that phosphorylation plays in Hh signal transduction, and discuss the conservation and difference between Drosophila and mammalian Hh signaling mechanisms. ..
  28. 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...
  29. Chen C, von Kessler D, Park W, Wang B, Ma Y, Beachy P. Nuclear trafficking of Cubitus interruptus in the transcriptional regulation of Hedgehog target gene expression. Cell. 1999;98:305-16 pubmed
    ..Even in the absence of signaling, nuclear accumulation of Ci155 suffices for significant induction of Hh targets, and active nuclear export of Ci155 is an essential mechanism for maintenance of the unstimulated state. ..
  30. 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
    ..Cubitus interruptus (Ci) is associated in a 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...
  31. 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 unclear how the ..
  32. 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)]...
  33. 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. ..
  34. 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...
  35. Hooper J. Smoothened translates Hedgehog levels into distinct responses. Development. 2003;130:3951-63 pubmed
    ..Thus, two activities of Smoothened translate different levels of Hedgehog into distinct intracellular responses. ..
  36. 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 ..
  37. 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)...
  38. Forbes A, Nakano Y, Taylor A, Ingham P. Genetic analysis of hedgehog signalling in the Drosophila embryo. Dev Suppl. 1993;:115-24 pubmed
    ..We have also found that transcription of patched is regulated by the same pathway and describe the identification of cis-acting upstream elements of the ptc transcription unit that mediate this regulation. ..
  39. Fan J, Liu Y, Jia J. Hh-induced Smoothened conformational switch is mediated by differential phosphorylation at its C-terminal tail in a dose- and position-dependent manner. Dev Biol. 2012;366:172-84 pubmed publisher
    ..a gradual conformational change in the Smo cytoplasmic tail, which promotes the interaction between Smo and Costal2 (Cos2). Moreover, we show that Hh regulates both PKA and CK1 phosphorylation of Smo...
  40. 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...
  41. 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 proteins are still ..
  42. 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
    ..corresponds to embryonic and adult anomalies similar to those displayed by the segment polarity mutant costal-2 (cos-2). Class II alleles are recessive to class I alleles in a fu[I]/fu[II];Su(fu)/Su(fu) combination...
  43. 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
    ..least three genes: fused (a protein-serine/threonine kinase), cubitus interruptus (a transcription factor), and costal2 (a kinesin-like protein)...
  44. 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
    ..We propose that FU could act as a switch, activator in presence of HH signal or inhibitor in absence of HH. ..
  45. 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. ..
  46. 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
    ..we provide evidence that Smo signals 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 ..
  47. 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
    ..We propose that the Fu C-terminal domain can differentially regulate the Fu catalytic domain according to cell position in the parasegment. ..
  48. 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.
  49. 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. ..
  50. Klingensmith J, Nusse R. Signaling by wingless in Drosophila. Dev Biol. 1994;166:396-414 pubmed
    ..Where appropriate, wingless signaling will be compared to the activity of vertebrate Wnt proteins. ..
  51. Kornberg T. The contrasting roles of primary cilia and cytonemes in Hh signaling. Dev Biol. 2014;394:1-5 pubmed publisher
    ..Implicit in this model is the idea that initial binding and uptake of Hh is independent of and segregated from the processes of signal transduction and activation. ..
  52. 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. ..
  53. Perrimon N. Hedgehog and beyond. Cell. 1995;80:517-20 pubmed
  54. Christiansen A, Ding T, Fan Y, Graves H, Herz H, Lindblad J, et al. Non-cell autonomous control of apoptosis by ligand-independent Hedgehog signaling in Drosophila. Cell Death Differ. 2013;20:302-11 pubmed publisher
    ..This non-cell autonomous control of apoptosis highlights an underappreciated function of deregulated Hh signaling, which may help to generate a supportive micro-environment for tumor development. ..
  55. van den Heuvel M, Klingensmith J, Perrimon N, Nusse R. Cell patterning in the Drosophila segment: engrailed and wingless antigen distributions in segment polarity mutant embryos. Dev Suppl. 1993;:105-14 pubmed
    ..Using double mutant embryos, epistatic relationships between some segment polarity genes have been established. We present a model showing a current view of segment polarity gene interactions. ..
  56. Ranieri N, Thérond P, Ruel L. Switch of PKA substrates from Cubitus interruptus to Smoothened in the Hedgehog signalosome complex. Nat Commun. 2014;5:5034 pubmed publisher
    ..We propose a new model in which the PKA is constitutively present and active within the HSC, and in which the relative levels of Ci and Smo within the HSC determine differential activation and cellular response to Hh signalling. ..
  57. Zadorozny E, Little J, Kalderon D. Contributions of Costal 2-Fused interactions to Hedgehog signaling in Drosophila. Development. 2015;142:931-42 pubmed publisher
    The Drosophila kinesin-family protein Costal 2 (Cos2) and its mammalian ortholog Kif7 play dual roles in Hedgehog (Hh) signaling...