Gene Symbol: smo
Description: smoothened
Alias: CG11561, Dmel\CG11561, SMO, Smo, dSmo, smoothened, CG11561-PA, smo-PA, smooth, smoothene
Species: fruit fly
Products:     smo

Top Publications

  1. Nedelcu D, Liu J, Xu Y, Jao C, Salic A. Oxysterol binding to the extracellular domain of Smoothened in Hedgehog signaling. Nat Chem Biol. 2013;9:557-64 pubmed publisher
    Oxysterols bind the seven-transmembrane protein Smo (Smo) and potently activate vertebrate Hedgehog (Hh) signaling, a pathway essential in embryonic development, adult stem cell maintenance and cancer...
  2. Sampedro J, Johnston P, Lawrence P. A role for wingless in the segmental gradient of Drosophila?. Development. 1993;117:677-87 pubmed
    ..We propose an alternative hypothesis that the wild-type function of the wingless protein is to maintain and 'seal' the parasegment borders; in its absence the borders fail to isolate abutting segmental gradients. ..
  3. Alcedo J, Zou Y, Noll M. Posttranscriptional regulation of smoothened is part of a self-correcting mechanism in the Hedgehog signaling system. Mol Cell. 2000;6:457-65 pubmed
    Hedgehog signaling, mediated through its Patched-Smoothened receptor complex, is essential for pattern formation in animal development...
  4. Hooper J. Smoothened translates Hedgehog levels into distinct responses. Development. 2003;130:3951-63 pubmed
    ..Hedgehog regulates this balance through its receptor, Patched, which acts through Smoothened and thence a regulatory complex that includes Fused, Costal, Suppressor of Fused and Cubitus interruptus...
  5. Jiang J, Struhl G. Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb. Nature. 1998;391:493-6 pubmed
  6. Lu X, Liu S, Kornberg T. The C-terminal tail of the Hedgehog receptor Patched regulates both localization and turnover. Genes Dev. 2006;20:2539-51 pubmed
    ..These data show that degradation of Ptc is regulated at a step subsequent to endocytosis, although endocytosis is a likely prerequisite. We also show that the CTD of mouse Ptc regulates turnover. ..
  7. Kent D, Bush E, Hooper J. Roadkill attenuates Hedgehog responses through degradation of Cubitus interruptus. Development. 2006;133:2001-10 pubmed
    ..The existence of human orthologs for Rdx raises the possibility that this novel feedback loop also modulates Hh responses in humans. ..
  8. Tanaka Matakatsu M, Du W. Direct control of the proneural gene atonal by retinal determination factors during Drosophila eye development. Dev Biol. 2008;313:787-801 pubmed
    ..These results demonstrate a direct mechanism by which the RD factors regulate ato expression and suggest an important role of Dpp in the activation of ato 3' enhancer is to regulate the levels of RD factors. ..
  9. 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
    ..Their principal target appears to be Smoothened (Smo), the intracellular signal-generating component of the pathway and a member of the G-protein-coupled ..

More Information


  1. Price M, Kalderon D. Proteolysis of the Hedgehog signaling effector Cubitus interruptus requires phosphorylation by Glycogen Synthase Kinase 3 and Casein Kinase 1. Cell. 2002;108:823-35 pubmed
    ..Conversely, Ci-155 levels are reduced in Hedgehog-responding cells by overexpression of PKA and the Drosophila CK1, Double-time, a regulator of circadian rhythms. ..
  2. Pappu K, Chen R, Middlebrooks B, Woo C, Heberlein U, Mardon G. Mechanism of hedgehog signaling during Drosophila eye development. Development. 2003;130:3053-62 pubmed
    ..Moreover, while the effects of Hh are primarily concentration dependent in other tissues, hh signaling in the eye acts as a binary switch to initiate retinal morphogenesis by inducing expression of the tissue-specific factor Eya. ..
  3. 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
    The seven-transmembrane protein Smoothened (Smo) transduces extracellular activation of the Hedgehog (Hh) pathway by an unknown mechanism to increase transcriptional activity of the latent cytoplasmic transcription factor Ci (Cubitus ..
  4. 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 seven-transmembrane protein Smoothened (Smo) acts as a signal transducer in the Hedgehog (Hh) pathway that mediates many key developmental processes...
  5. Cavodeassi F, Diez Del Corral R, Campuzano S, Dominguez M. Compartments and organising boundaries in the Drosophila eye: the role of the homeodomain Iroquois proteins. Development. 1999;126:4933-42 pubmed
  6. Methot N, Basler K. Hedgehog controls limb development by regulating the activities of distinct transcriptional activator and repressor forms of Cubitus interruptus. Cell. 1999;96:819-31 pubmed
    ..These different activities of Ci regulate overlapping but distinct subsets of Hh target genes. Thus, limb development is organized by the integration of different transcriptional outputs of Hh signaling. ..
  7. 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
    ..HH signal controls the traffic and activity of the seven-pass transmembrane protein Smoothened (SMO), leading to the transcriptional regulation of HH-responsive genes...
  8. Martin V, Carrillo G, Torroja C, Guerrero I. The sterol-sensing domain of Patched protein seems to control Smoothened activity through Patched vesicular trafficking. Curr Biol. 2001;11:601-7 pubmed
    ..Ptc(SSD) protein shows dominant-negative activity in blocking Hh signaling by preventing the downregulation of Smoothened (Smo), a positive effector of the Hh pathway...
  9. Ogden S, Ascano M, Stegman M, Robbins D. Regulation of Hedgehog signaling: a complex story. Biochem Pharmacol. 2004;67:805-14 pubmed
    ..Ci is regulated through communication of the membrane proteins Patched (Ptc) and Smoothened (Smo) to the intracellular Hedgehog Signaling Complex (HSC) in response to a graded concentration of Hh ligand...
  10. Landsberg K, Farhadifar R, Ranft J, Umetsu D, Widmann T, Bittig T, et al. Increased cell bond tension governs cell sorting at the Drosophila anteroposterior compartment boundary. Curr Biol. 2009;19:1950-5 pubmed publisher
    ..Our results provide a physical mechanism in which the local increase in Myosin II-dependent cell bond tension directs cell sorting at compartment boundaries. ..
  11. Torroja C, Gorfinkiel N, Guerrero I. Patched controls the Hedgehog gradient by endocytosis in a dynamin-dependent manner, but this internalization does not play a major role in signal transduction. Development. 2004;131:2395-408 pubmed
  12. Zhang Y, Kalderon D. Regulation of cell proliferation and patterning in Drosophila oogenesis by Hedgehog signaling. Development. 2000;127:2165-76 pubmed
    ..Somatic cells in the ovary cannot proliferate normally in the absence of Hh or Smoothened activity...
  13. Curtiss J, Mlodzik M. Morphogenetic furrow initiation and progression during eye development in Drosophila: the roles of decapentaplegic, hedgehog and eyes absent. Development. 2000;127:1325-36 pubmed
    ..Interestingly, furrow-associated expression of eya, so and dac is not affected by double mutant tissue, suggesting that some other factor(s) regulates their expression during furrow progression. ..
  14. 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
    ..transduces signal by regulating the subcellular localization and conformational state of the GPCR-like protein Smoothened (Smo) but how Smo relays the signal to cytoplasmic signaling components remains poorly understood...
  15. Strigini M, Cohen S. A Hedgehog activity gradient contributes to AP axial patterning of the Drosophila wing. Development. 1997;124:4697-705 pubmed
    ..Comparing the biological activities of secreted and membrane-tethered Hh provides evidence that Hh forms a local concentration gradient and functions as a concentration-dependent morphogen in the fly wing. ..
  16. Li S, Chen Y, Shi Q, Yue T, Wang B, Jiang J. Hedgehog-regulated ubiquitination controls smoothened trafficking and cell surface expression in Drosophila. PLoS Biol. 2012;10:e1001239 pubmed publisher
    Hedgehog transduces signal by promoting cell surface expression of the seven-transmembrane protein Smoothened (Smo) in Drosophila, but the underlying mechanism remains unknown...
  17. Jia H, Liu Y, Xia R, Tong C, Yue T, Jiang J, et al. Casein kinase 2 promotes Hedgehog signaling by regulating both smoothened and Cubitus interruptus. J Biol Chem. 2010;285:37218-26 pubmed publisher
    ..inactivation of CK2 by CK2? RNAi enhances the loss-of-Hh wing phenotype induced by a dominant negative form of Smoothened (Smo)...
  18. 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. ..
  19. 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
    The activation of Smoothened (Smo) requires phosphorylation at three clusters of Serine residues in Drosophila Hedgehog (Hh) signaling...
  20. Denef N, Neubüser D, Perez L, Cohen S. Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened. Cell. 2000;102:521-31 pubmed
    ..Patched functions in Hedgehog binding, and Smoothened functions in transducing the signal...
  21. Mukai A, Yamamoto Hino M, Awano W, Watanabe W, Komada M, Goto S. Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt. EMBO J. 2010;29:2114-25 pubmed publisher
    ..These results unveil a novel mechanism that regulates the cellular responsiveness to Wg/Wnt by controlling the cell surface level of Frizzled. ..
  22. Greenwood S, Struhl G. Progression of the morphogenetic furrow in the Drosophila eye: the roles of Hedgehog, Decapentaplegic and the Raf pathway. Development. 1999;126:5795-808 pubmed
  23. 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 propose that Hh induces target gene expression by a two-step mechanism in which Ci[act] is first formed and then accumulates in the nucleus via Fu-induced neutralization of Su(fu) activity. ..
  24. Stone D, Hynes M, Armanini M, Swanson T, Gu Q, Johnson R, et al. The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature. 1996;384:129-34 pubmed
    ..We show that Ptc can form a physical complex with a newly cloned vertebrate homologue of the Drosophila protein Smoothened (vSmo), and that vSmo is coexpressed with vPtc in many tissues but does not bind Shh directly...
  25. Deshpande G, Swanhart L, Chiang P, Schedl P. Hedgehog signaling in germ cell migration. Cell. 2001;106:759-69 pubmed
    ..Misexpression of hh in the soma induces germ cells to migrate to inappropriate locations. Conversely, cell-autonomous components of the hh pathway appear to be required in the germline for proper germ cell migration. ..
  26. 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
    ..differences exist between Drosophila and vertebrates in the way signals are transduced from the membrane protein Smoothened (Smo) to the Ci/Gli transcription factors...
  27. Chen J, Taipale J, Cooper M, Beachy P. Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev. 2002;16:2743-8 pubmed
    ..that this inhibitory effect is mediated by direct binding of cyclopamine to the heptahelical bundle of Smoothened (Smo)...
  28. Xia R, Jia H, Fan J, Liu Y, Jia J. USP8 promotes smoothened signaling by preventing its ubiquitination and changing its subcellular localization. PLoS Biol. 2012;10:e1001238 pubmed publisher
    The seven transmembrane protein Smoothened (Smo) is a critical component of the Hedgehog (Hh) signaling pathway and is regulated by phosphorylation, dimerization, and cell-surface accumulation upon Hh stimulation...
  29. Zhao Y, Tong C, Jiang J. Hedgehog regulates smoothened activity by inducing a conformational switch. Nature. 2007;450:252-8 pubmed
    Hedgehog (HH) morphogen is essential for metazoan development. The seven-transmembrane protein smoothened (SMO) transduces the HH signal across the plasma membrane, but how SMO is activated remains poorly understood...
  30. Chen Y, Jiang J. Decoding the phosphorylation code in Hedgehog signal transduction. Cell Res. 2013;23:186-200 pubmed publisher
    ..Binding of Hh to Patched (Ptc), a twelve-transmembrane protein, alleviates its inhibition of Smoothened (Smo), a seven-transmembrane protein related to G-protein-coupled receptors (GPCRs), leading to Smo ..
  31. Firth L, Bhattacharya A, Baker N. Cell cycle arrest by a gradient of Dpp signaling during Drosophila eye development. BMC Dev Biol. 2010;10:28 pubmed publisher
    ..G1 arrest is specific for one competent domain in the eye disc, allowing Dpp signaling to promote growth at earlier developmental stages. ..
  32. Escudero L, Freeman M. Mechanism of G1 arrest in the Drosophila eye imaginal disc. BMC Dev Biol. 2007;7:13 pubmed
    ..The unexpectedly complex network of regulation may reflect the importance of cells being uniformly ready to respond to the inductive signals that coordinate retinal differentiation. ..
  33. Ohlmeyer J, Kalderon D. Dual pathways for induction of wingless expression by protein kinase A and Hedgehog in Drosophila embryos. Genes Dev. 1997;11:2250-8 pubmed
    ..transcription of specific genes by an unknown mechanism that requires the serpentine transmembrane protein Smoothened (Smo) and the transcription factor Cubitus interruptus (Ci)...
  34. Lopes C, Casares F. hth maintains the pool of eye progenitors and its downregulation by Dpp and Hh couples retinal fate acquisition with cell cycle exit. Dev Biol. 2010;339:78-88 pubmed publisher
    ..We integrate these results in a model of the early steps of eye development that links proliferation control and differential gene expression with patterning signals. ..
  35. Fu W, Baker N. Deciphering synergistic and redundant roles of Hedgehog, Decapentaplegic and Delta that drive the wave of differentiation in Drosophila eye development. Development. 2003;130:5229-39 pubmed
    ..Notch acted in part through downregulation of Hairy; Hh signaling downregulated Hairy independently of Notch. One feature of this signaling network is to limit Dpp signaling spatially to a range coincident with Hh. ..
  36. Kalderon D. Similarities between the Hedgehog and Wnt signaling pathways. Trends Cell Biol. 2002;12:523-31 pubmed
    ..This review compares the two pathways to explore whether our more extensive knowledge of Wnt pathways can be of predictive value for investigating Hedgehog signaling. ..
  37. Camp D, Currie K, Labbe A, van Meyel D, Charron F. Ihog and Boi are essential for Hedgehog signaling in Drosophila. Neural Dev. 2010;5:28 pubmed publisher
    ..We found that ihog and boi are required for the accumulation of the essential Hh signaling mediator Smoothened (Smo) in Hh-responsive cells, providing evidence that Ihog and Boi act upstream of Smo in the Hh signaling ..
  38. 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
    ..The mechanism by which Kurtz antagonises Hedgehog signalling is to promote Smoothened internalization and degradation in a clathrin- and proteosomal-dependent manner...
  39. Gritzan U, Hatini V, DiNardo S. Mutual antagonism between signals secreted by adjacent wingless and engrailed cells leads to specification of complementary regions of the Drosophila parasegment. Development. 1999;126:4107-15 pubmed
    ..Here cells differentiate into smooth cuticle or distinct denticle types...
  40. 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
    ..All Hh responses require the seven transmembrane domain protein Smoothened, which itself becomes hyperphosphorylated during Hh signalling...
  41. 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. ..
  42. Deshpande G, Schedl P. HMGCoA reductase potentiates hedgehog signaling in Drosophila melanogaster. Dev Cell. 2005;9:629-38 pubmed
    ..while the adjacent "Hh-receiving" cells cannot sustain wg expression and fail to relocalize the Smoothened (Smo) receptor...
  43. Yao S, Lum L, Beachy P. The ihog cell-surface proteins bind Hedgehog and mediate pathway activation. Cell. 2006;125:343-57 pubmed
  44. 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
    ..In both cases, Hh signaling proceeds through the activation of the seven-transmembrane protein Smoothened (Smo), which is thought to convert the Gli family of transcription factors from transcriptional repressors to ..
  45. 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. ..
  46. van den Heuvel M, Ingham P. smoothened encodes a receptor-like serpentine protein required for hedgehog signalling. Nature. 1996;382:547-51 pubmed
    ..Here we show that the segment-polarity gene smoothened is required for the response of cells to hedgehog signalling during the development of both the embryonic ..
  47. 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 of the transcriptional activity of Ci in the absence of ligand...
  48. 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
    ..transduction is initiated when Hh binds to its receptor Patched (Ptc), activating the transmembrane protein Smoothened (Smo). Smo transmits its activation signal to a microtubule-associated Hedgehog signaling complex (HSC)...
  49. Vrailas A, Moses K. Smoothened, thickveins and the genetic control of cell cycle and cell fate in the developing Drosophila eye. Mech Dev. 2006;123:151-65 pubmed
    ..Here we have used the mosaic clone analysis of null mutations of the smoothened and thickveins genes (which encode the receptors for these two signals) both alone and in combination, to study ..
  50. Jia J, Zhang L, Zhang Q, Tong C, Wang B, Hou F, et al. Phosphorylation by double-time/CKIepsilon and CKIalpha targets cubitus interruptus for Slimb/beta-TRCP-mediated proteolytic processing. Dev Cell. 2005;9:819-30 pubmed
    ..We propose that phosphorylation of Ci by CKI creates multiple Slimb/beta-TRCP binding sites that act cooperatively to recruit SCF(Slimb/beta-TRCP). ..
  51. Kirilly D, Spana E, Perrimon N, Padgett R, Xie T. BMP signaling is required for controlling somatic stem cell self-renewal in the Drosophila ovary. Dev Cell. 2005;9:651-62 pubmed
    ..Our work further suggests that BMP signaling could promote self-renewal of adult stem cells in other systems. ..
  52. 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
    ..In addition, we demonstrate that Cos2 associates with membranes in cells that lack the transmembrane protein Smoothened (Smo) through a domain of Cos2 distinct from its recently characterized Smo binding domain...
  53. Christiansen A, Ding T, Bergmann A. Ligand-independent activation of the Hedgehog pathway displays non-cell autonomous proliferation during eye development in Drosophila. Mech Dev. 2012;129:98-108 pubmed publisher
    ..Loss of Patched or activation of Smoothened in mouse models increases the occurrence of tumors...
  54. 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
    ..of main morphogens during metazoan development, the graded Hh signal is transduced across the plasma membrane by Smoothened (Smo) through the differential phosphorylation of its cytoplasmic tail, leading to pathway activation and the ..
  55. Hartman T, Zinshteyn D, Schofield H, Nicolas E, Okada A, O Reilly A. Drosophila Boi limits Hedgehog levels to suppress follicle stem cell proliferation. J Cell Biol. 2010;191:943-52 pubmed publisher
    ..Our studies demonstrate that cells distant from the local niche can regulate stem cell function through ligand sequestration, a mechanism that likely is conserved in other epithelial tissues. ..
  56. Østerlund T, Kogerman P. Hedgehog signalling: how to get from Smo to Ci and Gli. Trends Cell Biol. 2006;16:176-80 pubmed
    ..Hedgehog elicits a signalling response that activates Smoothened (Smo)...
  57. Thérond P, Limbourg Bouchon B, Gallet A, Dussilol F, Pietri T, van den Heuvel M, et al. Differential requirements of the fused kinase for hedgehog signalling in the Drosophila embryo. Development. 1999;126:4039-51 pubmed
    ..pathway only in anterior, wingless-expressing cells we could show that the Hedgehog signalling components Smoothened and Cubitus interruptus are required in cells posterior to Hedgehog domain to maintain patched expression ..
  58. Lum L, Beachy P. The Hedgehog response network: sensors, switches, and routers. Science. 2004;304:1755-9 pubmed
    ..signal transmission from membrane to cytoplasm proceeds through recruitment, by the seven-transmembrane protein Smoothened, of an atypical kinesin, which routes pathway activation by interaction with other components of a complex that ..
  59. Ohlmeyer J, Kalderon D. Hedgehog stimulates maturation of Cubitus interruptus into a labile transcriptional activator. Nature. 1998;396:749-53 pubmed
  60. 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
    ..Hh pathway activity is absolutely dependent on signalling by the seven-transmembrane protein smoothened (Smo), which is regulated by the Hh receptor patched (Ptc)...
  61. CARROLL C, Marada S, Stewart D, Ouyang J, Ogden S. The extracellular loops of Smoothened play a regulatory role in control of Hedgehog pathway activation. Development. 2012;139:612-21 pubmed publisher
    ..Ligand-induced pathway activation requires signaling by the transmembrane protein Smoothened (Smo), a member of the G-protein-coupled receptor (GPCR) superfamily...
  62. Gallet A, Staccini Lavenant L, Therond P. Cellular trafficking of the glypican Dally-like is required for full-strength Hedgehog signaling and wingless transcytosis. Dev Cell. 2008;14:712-25 pubmed publisher
    ..Thus, Dlp endocytosis is a common regulatory mechanism of both Hh and Wg morphogen action. ..
  63. 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. ..
  64. 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. ..
  65. Amanai K, Jiang J. Distinct roles of Central missing and Dispatched in sending the Hedgehog signal. Development. 2001;128:5119-27 pubmed
    ..Finally, we show that cmn mutations bear molecular lesions in CG11495, which encodes a putative membrane bound acyltransferase related to Porcupine, a protein implicated in regulating the secretion of Wingless (Wg) signal. ..
  66. Vied C, Reilein A, Field N, Kalderon D. Regulation of stem cells by intersecting gradients of long-range niche signals. Dev Cell. 2012;23:836-48 pubmed publisher
  67. Cheng S, Maier D, Neubueser D, Hipfner D. Regulation of smoothened by Drosophila G-protein-coupled receptor kinases. Dev Biol. 2010;337:99-109 pubmed publisher
    ..Cytoplasmic signaling is initiated by Smoothened (Smo), a G-protein-coupled receptor (GPCR) family member, whose levels and activity are regulated by the Hh ..
  68. Chen M, Wilson C, Li Y, Law K, Lu C, Gacayan R, et al. Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved. Genes Dev. 2009;23:1910-28 pubmed publisher
    ..In contrast, fly Smo is unable to translocate to the primary cilium and activate the mammalian Hh pathway...
  69. Nakano Y, Nystedt S, Shivdasani A, Strutt H, Thomas C, Ingham P. Functional domains and sub-cellular distribution of the Hedgehog transducing protein Smoothened in Drosophila. Mech Dev. 2004;121:507-18 pubmed
    ..The serpentine protein Smoothened (Smo) is essential for cells to respond to the Hedeghog (Hh) signal; oncogenic forms of Smo have been isolated ..
  70. Shi D, Lv X, Zhang Z, Yang X, Zhou Z, Zhang L, et al. Smoothened oligomerization/higher order clustering in lipid rafts is essential for high Hedgehog activity transduction. J Biol Chem. 2013;288:12605-14 pubmed publisher
    ..signal reception system that includes two membrane proteins, the receptor Patched (Ptc) and the transducer Smoothened (Smo)...
  71. Alcedo J, Ayzenzon M, Von Ohlen T, Noll M, Hooper J. The Drosophila smoothened gene encodes a seven-pass membrane protein, a putative receptor for the hedgehog signal. Cell. 1996;86:221-32 pubmed
    b>Smoothened (smo) is a segment polarity gene required for correct patterning of every segment in Drosophila...
  72. Albert R, Othmer H. The topology of the regulatory interactions predicts the expression pattern of the segment polarity genes in Drosophila melanogaster. J Theor Biol. 2003;223:1-18 pubmed
    ..The model gives important insights into the functioning of the segment polarity gene network, such as the crucial role of the wingless and sloppy paired genes, and the network's ability to correct errors in the pre-pattern. ..
  73. Baker N, Bhattacharya A, Firth L. Regulation of Hh signal transduction as Drosophila eye differentiation progresses. Dev Biol. 2009;335:356-66 pubmed publisher
    ..A model is presented for regulation of the Cullin-3 and Cullin-1 pathways that modifies Hedgehog signaling as the morphogenetic furrow moves and the responses of retinal cells change. ..
  74. Lawrence P, Casal J, Struhl G. The hedgehog morphogen and gradients of cell affinity in the abdomen of Drosophila. Development. 1999;126:2441-9 pubmed
    ..Within the P compartment we found some evidence for a U-shaped gradient of affinity, but this cannot be due to Hedgehog which does not act in the P compartment. ..
  75. Baonza A, Freeman M. Control of cell proliferation in the Drosophila eye by Notch signaling. Dev Cell. 2005;8:529-39 pubmed
    ..Delta to Notch signaling derepresses the inhibition of dE2F1 by RBF, and Delta expression depends on the secreted proteins Hedgehog and Dpp. Notch is also required for the expression of Cyclin A in the SMW. ..
  76. Firth L, Baker N. Extracellular signals responsible for spatially regulated proliferation in the differentiating Drosophila eye. Dev Cell. 2005;8:541-51 pubmed
    ..These studies identify the specific extracellular signals that pattern the retinal cell cycles and show how differentiation can be uncoupled from cell cycle exit. ..
  77. 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
    ..The seven-transmembrane protein Smoothened (Smo) transduces the Hh signal in both vertebrates and invertebrates; however, the mechanism of its action ..
  78. Végh M, Basler K. A genetic screen for hedgehog targets involved in the maintenance of the Drosophila anteroposterior compartment boundary. Genetics. 2003;163:1427-38 pubmed
    ..Among these, we identified a class of patched (ptc) alleles exhibiting a novel phenotype. These results demonstrate the value of our setup in the identification of genes involved in distinct wing-patterning processes. ..
  79. Dahmann C, Basler K. Opposing transcriptional outputs of Hedgehog signaling and engrailed control compartmental cell sorting at the Drosophila A/P boundary. Cell. 2000;100:411-22 pubmed
    ..We propose that the opposing transcriptional activities of Ci and En control cell segregation at the A/P boundary by regulating a single cell adhesion molecule. ..
  80. Murone M, Rosenthal A, de Sauvage F. Hedgehog signal transduction: from flies to vertebrates. Exp Cell Res. 1999;253:25-33 pubmed
    ..In the following review, we will not discuss in detail the role of Hh as a morphogen, but rather focus on its signal transduction pathway and its role in various human disorders. ..
  81. Chen Y, Struhl G. In vivo evidence that Patched and Smoothened constitute distinct binding and transducing components of a Hedgehog receptor complex. Development. 1998;125:4943-8 pubmed
    ..Hedgehog is bound and transduced by a receptor complex that includes Smoothened (Smo), a member of the Frizzled (Fz) family of seven-pass transmembrane receptors, as well as the multiple-pass ..
  82. 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
    ..COS2 is cytoplasmic and binds microtubules. We find that CI associates with COS2 in a large protein complex, suggesting that COS2 directly controls the activity of CI. ..
  83. Yang X, Mao F, Lv X, Zhang Z, Fu L, Lu Y, et al. Drosophila Vps36 regulates Smo trafficking in Hedgehog signaling. J Cell Sci. 2013;126:4230-8 pubmed publisher
    ..The seven-transmembrane domain protein Smoothened (Smo) is a key transducer of the Hh signaling pathway, and mediates the graded Hh signal across the cell plasma ..
  84. Vied C, Kalderon D. Hedgehog-stimulated stem cells depend on non-canonical activity of the Notch co-activator Mastermind. Development. 2009;136:2177-86 pubmed publisher
    ..Loss of Mam reduces the expression of a Hh pathway reporter in FSCs but not in wing discs, suggesting that Mam might enhance Hh signaling specifically in stem cells of the Drosophila ovary. ..
  85. Suzuki T, Saigo K. Transcriptional regulation of atonal required for Drosophila larval eye development by concerted action of eyes absent, sine oculis and hedgehog signaling independent of fused kinase and cubitus interruptus. Development. 2000;127:1531-40 pubmed
  86. Atkins M, Jiang Y, Sansores Garcia L, Jusiak B, Halder G, Mardon G. Dynamic rewiring of the Drosophila retinal determination network switches its function from selector to differentiation. PLoS Genet. 2013;9:e1003731 pubmed publisher
    ..We conclude that changes in the regulatory relationships among members of the retinal determination gene network are a driving force for key transitions in retinal development. ..