Gene Symbol: Smox
Description: Smad on X
Alias: CG2262, DSMAD2, DSmad2, Dmel\CG2262, SMAD2, SMOX, Sad, Smad, Smad2, SmoX, dSMAD2, dSmad2, dsmad2, l(1)G0348, sad, smad2, smox, ted, tmp, smad on X, CG2262-PA, CG2262-PB, Smox-PA, Smox-PB, Smox/dSmad2, sisters against dpp, temporarily deranged
Species: fruit fly
Products:     Smox

Top Publications

  1. Brummel T, Abdollah S, Haerry T, Shimell M, Merriam J, Raftery L, et al. The Drosophila activin receptor baboon signals through dSmad2 and controls cell proliferation but not patterning during larval development. Genes Dev. 1999;13:98-111 pubmed
    ..Furthermore, we identify a new Drosophila Smad, termed dSmad2, that is most closely related to vertebrate Smads 2 and 3...
  2. Zhang Y, Derynck R. Regulation of Smad signalling by protein associations and signalling crosstalk. Trends Cell Biol. 1999;9:274-9 pubmed
    ..Following receptor-induced activation, heteromeric Smad complexes translocate into the nucleus, where they act as transcription factors...
  3. Parker L, Ellis J, Nguyen M, Arora K. The divergent TGF-beta ligand Dawdle utilizes an activin pathway to influence axon guidance in Drosophila. Development. 2006;133:4981-91 pubmed
    ..that Daw initiates an activin signaling pathway via the receptors Punt and Baboon (Babo) and the signal-transducer Smad2. Furthermore, mutations in these signaling components display similar axon guidance defects...
  4. Zhu C, Boone J, Jensen P, Hanna S, Podemski L, Locke J, et al. Drosophila Activin- and the Activin-like product Dawdle function redundantly to regulate proliferation in the larval brain. Development. 2008;135:513-21 pubmed publisher that the same two ligands act redundantly through the Activin receptor Babo and its transcriptional mediator Smad2 (Smox), to regulate neuroblast numbers and proliferation rates in the developing larval brain...
  5. Jensen P, Zheng X, Lee T, O Connor M. The Drosophila Activin-like ligand Dawdle signals preferentially through one isoform of the Type-I receptor Baboon. Mech Dev. 2009;126:950-7 pubmed publisher
    ..These results reveal a mechanism by which distinct cell types can discriminate between different Activin-type signals during development as a result of differential expression of Type-I receptor isoforms. ..
  6. Peterson A, O Connor M. Activin receptor inhibition by Smad2 regulates Drosophila wing disc patterning through BMP-response elements. Development. 2013;140:649-59 pubmed publisher
    ..In our studies of TGF? superfamily signaling components, we found that a protein null mutation of Smad2, the only Activin subfamily R-Smad in the fruit fly, produces overgrown wing discs that resemble gain of function ..
  7. Peterson A, Jensen P, Shimell M, Stefancsik R, Wijayatonge R, Herder R, et al. R-Smad competition controls activin receptor output in Drosophila. PLoS ONE. 2012;7:e36548 pubmed publisher
    ..Type I receptor, can phosphorylate Mad, the BMP-specific R-Smad, in addition to its normal substrate, dSmad2. The Baboon-Mad activation appears direct because it occurs in the absence of canonical BMP Type I receptors...
  8. Ghosh A, O Connor M. Systemic Activin signaling independently regulates sugar homeostasis, cellular metabolism, and pH balance in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2014;111:5729-34 pubmed publisher
    ..We find that loss of canonical Smad signaling downstream of Daw leads to defects in sugar and systemic pH homeostasis...
  9. Henderson K, Andrew D. Identification of a novel Drosophila SMAD on the X chromosome. Biochem Biophys Res Commun. 1998;252:195-201 pubmed
    ..Here, we report the first identification of a novel Drosophila R-SMAD, which we have named Smox for Smad on X. We have localized the Smox gene to a specific interval on the X chromosome and shown that Smox is transcribed ..

More Information


  1. Bickel D, Shah R, Gesualdi S, Haerry T. Drosophila Follistatin exhibits unique structural modifications and interacts with several TGF-beta family members. Mech Dev. 2008;125:117-29 pubmed
    ..We find that mutants of daw are rescued in significant numbers by expression of vertebrate FS proteins. Since two PiggyBac insertions in dfs are not lethal, it appears that the function of dFS is non-essential or functionally redundant. ..
  2. Zheng X, Zugates C, Lu Z, Shi L, Bai J, Lee T. Baboon/dSmad2 TGF-beta signaling is required during late larval stage for development of adult-specific neurons. EMBO J. 2006;25:615-27 pubmed
    ..We found that Baboon(Babo)/dSmad2-mediated TGF-beta signaling, known to be essential for remodeling of larval functional neurons, is also ..
  3. Ellis J, Parker L, Cho J, Arora K. Activin signaling functions upstream of Gbb to regulate synaptic growth at the Drosophila neuromuscular junction. Dev Biol. 2010;342:121-33 pubmed publisher
    ..Mutants for Daw, the Activin type I receptor Baboon (Babo), and the signal transducer dSmad2, display reduced NMJ size suggesting that Daw utilizes a canonical Activin signal-transduction pathway in this ..
  4. Marquez R, Singer M, Takaesu N, Waldrip W, Kraytsberg Y, Newfeld S. Transgenic analysis of the Smad family of TGF-beta signal transducers in Drosophila melanogaster suggests new roles and new interactions between family members. Genetics. 2001;157:1639-48 pubmed
    b>Smad signal transducers are required for transforming growth factor-beta-mediated developmental events in many organisms including humans. However, the roles of individual human Smad genes (hSmads) in development are largely unknown...
  5. Das P, Inoue H, Baker J, Beppu H, Kawabata M, Harland R, et al. Drosophila dSmad2 and Atr-I transmit activin/TGFbeta signals. Genes Cells. 1999;4:123-34 pubmed
    ..Here we report the identification of dSmad2, a new Drosophila Smad which is most related to the activin/TGFbeta-pathway Smads, Smad2 and Smad3...
  6. Attisano L, Wrana J. Smads as transcriptional co-modulators. Curr Opin Cell Biol. 2000;12:235-43 pubmed
    The Smad signalling pathway is critical for transmitting transforming growth factor-beta (TGF-beta) superfamily signals from the cell surface to the nucleus...
  7. Tanimoto H, Itoh S, ten Dijke P, Tabata T. Hedgehog creates a gradient of DPP activity in Drosophila wing imaginal discs. Mol Cell. 2000;5:59-71 pubmed
    ..We suggest that regulation of tkv by HH is a key part of the mechanism that controls the level and distribution of DPP. ..
  8. Zheng X, Wang J, Haerry T, Wu A, Martin J, O Connor M, et al. TGF-beta signaling activates steroid hormone receptor expression during neuronal remodeling in the Drosophila brain. Cell. 2003;112:303-15 pubmed
    ..indistinguishable mutations affect Baboon function, a Drosophila TGF-beta/activin type I receptor, and dSmad2, its downstream transcriptional effector...
  9. Gesualdi S, Haerry T. Distinct signaling of Drosophila Activin/TGF-beta family members. Fly (Austin). 2007;1:212-21 pubmed
    ..We find that two potential ligands of BABO, Myoglianin (MYO) and Maverick (MAV), do not activate dSMAD2. Only Drosophila Activin (dACT) and the Activin-like ligand Dawdle (DAW) signal through BABO in combination with ..
  10. Massague J, Seoane J, Wotton D. Smad transcription factors. Genes Dev. 2005;19:2783-810 pubmed
    b>Smad transcription factors lie at the core of one of the most versatile cytokine signaling pathways in metazoan biology-the transforming growth factor-beta (TGFbeta) pathway...
  11. Barrio R, López Varea A, Casado M, de Celis J. Characterization of dSnoN and its relationship to Decapentaplegic signaling in Drosophila. Dev Biol. 2007;306:66-81 pubmed
    ..dSnoN does not interfere with Mad phosphorylation but it interacts genetically with Mad, Medea and dSmad2. Mutations in either the Smad2-3 or Smad4 putative binding sites of dSnoN prevent the antagonism of dSnoN towards ..
  12. Yang M, Nelson D, Funakoshi Y, Padgett R. Genome-wide microarray analysis of TGFbeta signaling in the Drosophila brain. BMC Dev Biol. 2004;4:14 pubmed
    ..Many of these genes are novel and several genes are implicated in growth control. Among the genes regulated by both pathways is ultraspiracle, which further connects TGFbeta with neuronal remodeling. ..
  13. Gibbens Y, Warren J, Gilbert L, O Connor M. Neuroendocrine regulation of Drosophila metamorphosis requires TGFbeta/Activin signaling. Development. 2011;138:2693-703 pubmed publisher
    ..As steroid hormone production in C. elegans and mammals is also influenced by TGF?/Activin signaling, this family of secreted factors may play a general role in regulating developmental transitions across phyla...
  14. Smith R, Machamer J, Kim N, Hays T, Marques G. Relay of retrograde synaptogenic signals through axonal transport of BMP receptors. J Cell Sci. 2012;125:3752-64 pubmed publisher
  15. Ting C, Herman T, Yonekura S, Gao S, Wang J, Serpe M, et al. Tiling of r7 axons in the Drosophila visual system is mediated both by transduction of an activin signal to the nucleus and by mutual repulsion. Neuron. 2007;56:793-806 pubmed
    ..This tiling function requires the Baboon ligand, dActivin, the transcription factor, dSmad2, and retrograde transport from the growth cone to the R7 nucleus...
  16. Raftery L, Sutherland D. TGF-beta family signal transduction in Drosophila development: from Mad to Smads. Dev Biol. 1999;210:251-68 pubmed
    ..Genetic studies of Dpp signaling led to the identification of Smad proteins as central mediators of signal transduction by TGF-beta family members...
  17. Takaesu N, Hyman Walsh C, Ye Y, Wisotzkey R, Stinchfield M, O Connor M, et al. dSno facilitates baboon signaling in the Drosophila brain by switching the affinity of Medea away from Mad and toward dSmad2. Genetics. 2006;174:1299-313 pubmed
    ..defects in the optic lobe of the brain very similar to those seen in baboon (Activin type I receptor) and dSmad2 mutants. This suggests that dSno is a mediator of Baboon signaling...
  18. Serpe M, O Connor M. The metalloprotease tolloid-related and its TGF-beta-like substrate Dawdle regulate Drosophila motoneuron axon guidance. Development. 2006;133:4969-79 pubmed
    ..Null mutants of daw, as well as mutations in its receptor babo and its downstream mediator Smad2, all exhibit axon guidance defects that are similar to but less severe than tlr...
  19. Hevia C, de Celis J. Activation and function of TGF? signalling during Drosophila wing development and its interactions with the BMP pathway. Dev Biol. 2013;377:138-53 pubmed publisher
    ..We found that the phosphorylation of Smad2, the specific transducer for TGF? signalling, occurs in a generalised manner in the wing disc...
  20. Koh Y, Rehfeld K, Ganetzky B. A Drosophila model of early onset torsion dystonia suggests impairment in TGF-beta signaling. Hum Mol Genet. 2004;13:2019-30 pubmed
    ..Consistent with this possibility, neuronal overexpression of Drosophila or human Smad2, a downstream effector of the TGF-beta pathway, suppressed the behavioral and ultrastructural defects of DeltaE ..
  21. Ayyaz A, Li H, Jasper H. Haemocytes control stem cell activity in the Drosophila intestine. Nat Cell Biol. 2015;17:736-48 pubmed publisher
    ..secrete the BMP homologue DPP, inducing ISC proliferation by activating the type I receptor Saxophone and the Smad homologue SMOX...
  22. Yu X, Gutman I, Mosca T, Iram T, Ozkan E, Garcia K, et al. Plum, an immunoglobulin superfamily protein, regulates axon pruning by facilitating TGF-? signaling. Neuron. 2013;78:456-68 pubmed publisher
  23. Mattila J, Havula E, Suominen E, Teesalu M, Surakka I, Hynynen R, et al. Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor Sugarbabe. Cell Rep. 2015;13:350-64 pubmed publisher
    ..In sum, Mondo-Mlx is a master regulator of other sugar-responsive pathways essential for adaptation to a high-sugar diet. ..
  24. Henderson K, Isaac D, Andrew D. Cell fate specification in the Drosophila salivary gland: the integration of homeotic gene function with the DPP signaling cascade. Dev Biol. 1999;205:10-21 pubmed
    ..tkv) gene and the type II receptor encoded by the punt (put) gene; two of the four known Drosophila members of the Smad family of proteins which transduce signals from the receptors to the nucleus, Mothers against dpp (Mad) and Medea (..
  25. Batut J, Schmierer B, Cao J, Raftery L, Hill C, Howell M. Two highly related regulatory subunits of PP2A exert opposite effects on TGF-beta/Activin/Nodal signalling. Development. 2008;135:2927-37 pubmed publisher
    ..Moreover, in Drosophila, overexpression of Smad2 rescues a severe wing phenotype caused by overexpression of the single Drosophila PP2A B subunit Twins...
  26. Li C, Guo Z, Wang Z. TGFbeta receptor saxophone non-autonomously regulates germline proliferation in a Smox/dSmad2-dependent manner in Drosophila testis. Dev Biol. 2007;309:70-7 pubmed
    ..Instead, Smox (Smad on X, Drosophila Smad2), the other receptor-Smad formerly characterized in TGFbeta/activin signaling, is necessary ..
  27. Pinto B, Wilmington S, Hornick E, Wallrath L, Geyer P. Tissue-specific defects are caused by loss of the Drosophila MAN1 LEM domain protein. Genetics. 2008;180:133-45 pubmed publisher
    ..Increased phospho-Smad staining in dMAN1 mutant wing discs is consistent with a role in transforming growth factor (TGF)-beta/bone ..
  28. Van Bortle K, Peterson A, Takenaka N, O Connor M, Corces V. CTCF-dependent co-localization of canonical Smad signaling factors at architectural protein binding sites in D. melanogaster. Cell Cycle. 2015;14:2677-87 pubmed publisher
    ..We have mapped Drosophila TGF-β signaling factors Mad, dSmad2, Medea, and Schnurri genome-wide in Kc cells and find that numerous sites for these factors overlap with the ..
  29. Lengil T, Gancz D, Gilboa L. Activin signaling balances proliferation and differentiation of ovarian niche precursors and enables adjustment of niche numbers. Development. 2015;142:883-92 pubmed publisher
    ..We propose that this mode of function allows Activin to balance proliferation and differentiation, and to equilibrate niche numbers. These results suggest a novel model for how niche numbers are corrected during development. ..
  30. Marinho J, Martins T, Neto M, Casares F, Pereira P. The nucleolar protein Viriato/Nol12 is required for the growth and differentiation progression activities of the Dpp pathway during Drosophila eye development. Dev Biol. 2013;377:154-65 pubmed publisher
    ..vito and members of the Dpp signaling pathway including the TGF-? receptors tkv (type I), put (type II), and the co-Smad medea (med)...
  31. Stronach B, Perrimon N. Activation of the JNK pathway during dorsal closure in Drosophila requires the mixed lineage kinase, slipper. Genes Dev. 2002;16:377-87 pubmed
    ..Furthermore, our results show that other putative JNKKKs cannot compensate for the loss of slpr function and, thus, may regulate other JNK or MAPK-dependent processes. ..
  32. Hyman C, Bartholin L, Newfeld S, Wotton D. Drosophila TGIF proteins are transcriptional activators. Mol Cell Biol. 2003;23:9262-74 pubmed
    ..We also demonstrate that Drosophila TGIF proteins physically interact with both Mad and dSmad2, suggesting a role in Dpp and activin signaling...
  33. Goldstein J, Kelly S, LoPresti P, Heydemann A, Earley J, Ferguson E, et al. SMAD signaling drives heart and muscle dysfunction in a Drosophila model of muscular dystrophy. Hum Mol Genet. 2011;20:894-904 pubmed publisher
    ..Increased SMAD signaling due to activation of the transforming growth factor-? (TGF?) pathway has been described in muscular ..
  34. Takaesu N, Stinchfield M, Shimizu K, Arase M, Quijano J, Watabe T, et al. Drosophila CORL is required for Smad2-mediated activation of Ecdysone Receptor expression in the mushroom body. Development. 2012;139:3392-401 pubmed publisher
    ..This is phenocopied in CORL-RNAi and Smad2-RNAi clones in wild-type larvae...
  35. Quijano J, Stinchfield M, Newfeld S. Wg signaling via Zw3 and mad restricts self-renewal of sensory organ precursor cells in Drosophila. Genetics. 2011;189:809-24 pubmed publisher
    ..phosphorylation sites in vertebrate homologs of Mad (Smads) suggests that this pathway, the first transforming growth factor ?-independent role for any Smad protein, may be widely utilized for regulating mitosis during development.
  36. Sorrentino G, Gillis W, Oomen Hajagos J, Thomsen G. Conservation and evolutionary divergence in the activity of receptor-regulated smads. Evodevo. 2012;3:22 pubmed publisher
    ..a secondary trunk axis in Xenopus embryos, whereas the orthologs from Xenopus (XSmad2 and XSmad3) and Drosophila (dSmad2) were capable of doing so...
  37. Grueber W, Jan Y. Dendritic development: lessons from Drosophila and related branches. Curr Opin Neurobiol. 2004;14:74-82 pubmed
    ..Here, we review some recent advances in our understanding of dendritic development in insects, focusing primarily on insights that have been gained from studies of Drosophila. ..
  38. Kulkarni M, Booker M, Silver S, Friedman A, Hong P, Perrimon N, et al. Evidence of off-target effects associated with long dsRNAs in Drosophila melanogaster cell-based assays. Nat Methods. 2006;3:833-8 pubmed
    ..Although a full appreciation of all causes of false positive errors remains to be determined, we suggest simple guidelines to help ensure high-quality information from RNAi high-throughput screens. ..
  39. Sander V, Eivers E, Choi R, De Robertis E. Drosophila Smad2 opposes Mad signaling during wing vein development. PLoS ONE. 2010;5:e10383 pubmed publisher
    ..In Drosophila, Mad regulates tissue determination and growth in the wing, but the function of dSmad2 in wing patterning is largely unknown...
  40. Quijano J, Stinchfield M, Zerlanko B, Gibbens Y, Takaesu N, Hyman Walsh C, et al. The Sno oncogene antagonizes Wingless signaling during wing development in Drosophila. PLoS ONE. 2010;5:e11619 pubmed publisher
  41. Hu J, Jiao D, Xu Q, Ying X, Liu W, Chi Q, et al. Identification of proteasome subunit beta type 2 associated with deltamethrin detoxification in Drosophila Kc cells by cDNA microarray analysis and bioassay analyses. Gene. 2016;582:85-93 pubmed publisher
    ..These detoxification results represent the first evidence that Prosbeta2 plays a role in the detoxification of DM, which may provide new idea and target for studying the molecular mechanisms of insect resistance. ..
  42. Lee Hoeflich S, Zhao X, Mehra A, Attisano L. The Drosophila type II receptor, Wishful thinking, binds BMP and myoglianin to activate multiple TGFbeta family signaling pathways. FEBS Lett. 2005;579:4615-21 pubmed
    ..Given that myoglianin is expressed in muscle and glial-derived cells, these results also suggest that Wit may mediate myoglianin-dependent signals in the nervous system. ..
  43. Bai H, Kang P, Hernandez A, Tatar M. Activin signaling targeted by insulin/dFOXO regulates aging and muscle proteostasis in Drosophila. PLoS Genet. 2013;9:e1003941 pubmed publisher
    ..Activin signaling through the Smad binding element inhibits the transcription of Autophagy-specific gene 8a (Atg8a) within muscle, a factor ..
  44. Kniss J, Holbrook S, Herman T. R7 photoreceptor axon growth is temporally controlled by the transcription factor Ttk69, which inhibits growth in part by promoting transforming growth factor-?/activin signaling. J Neurosci. 2013;33:1509-20 pubmed publisher
    ..We find that Ttk69 is required for normal activation of this pathway but that Ttk69 likely also inhibits R7 axon growth by a TGF-?/Activin-independent mechanism. ..
  45. Kamiya Y, Miyazono K, Miyazawa K. Specificity of the inhibitory effects of Dad on TGF-beta family type I receptors, Thickveins, Saxophone, and Baboon in Drosophila. FEBS Lett. 2008;582:2496-500 pubmed publisher
    ..In Drosophila, only one I-Smad, Dad, has been identified. Here we examined inhibitory effects of Dad on type I receptors in Drosophila...
  46. Zimmerman C, Padgett R. Transforming growth factor beta signaling mediators and modulators. Gene. 2000;249:17-30 pubmed
    ..More recent studies indicate that many other proteins serve as modulators of Smad activity, and utimately define specific cellular responses to TGFbeta...
  47. Nakayama T, Cui Y, Christian J. Regulation of BMP/Dpp signaling during embryonic development. Cell Mol Life Sci. 2000;57:943-56 pubmed
    ..Binding of BMP-4 or Dpp to its cognate receptor leads to phosphorylation of intracellular signal-transducing Smad proteins that then form hetero-oligomers, translocate to the nucleus and modulate transcription of target genes...
  48. Ting C, McQueen P, Pandya N, Lin T, Yang M, Reddy O, et al. Photoreceptor-derived activin promotes dendritic termination and restricts the receptive fields of first-order interneurons in Drosophila. Neuron. 2014;81:830-846 pubmed publisher
    ..We suggest that afferent-derived Activin regulates the dendritic field size of their postsynaptic partners to ensure appropriate synaptic partnership. ..
  49. Massague J, Wotton D. Transcriptional control by the TGF-beta/Smad signaling system. EMBO J. 2000;19:1745-54 pubmed
  50. Massague J, Chen Y. Controlling TGF-beta signaling. Genes Dev. 2000;14:627-44 pubmed
  51. Nedelsky N, Pennuto M, Smith R, Palazzolo I, Moore J, Nie Z, et al. Native functions of the androgen receptor are essential to pathogenesis in a Drosophila model of spinobulbar muscular atrophy. Neuron. 2010;67:936-52 pubmed publisher
    ..These findings indicate that SBMA pathogenesis is mediated by misappropriation of native protein function, a mechanism that may apply broadly to polyglutamine diseases...
  52. Kim M, O Connor M. Anterograde Activin signaling regulates postsynaptic membrane potential and GluRIIA/B abundance at the Drosophila neuromuscular junction. PLoS ONE. 2014;9:e107443 pubmed publisher
    ..We find that elimination of the Activin/TGF-β type I receptor babo, or its downstream signal transducer smox, does not affect presynaptic NMJ growth or evoked excitatory junctional potentials (EJPs), but instead results in a ..
  53. Liang Y, Lin X, Liang M, Brunicardi F, Ten Dijke P, Chen Z, et al. dSmurf selectively degrades decapentaplegic-activated MAD, and its overexpression disrupts imaginal disc development. J Biol Chem. 2003;278:26307-10 pubmed
    ..We conclude that dSmurf specifically targets phosphorylated MAD to proteasome-dependent degradation and regulates DPP signaling during development. ..