Wnt signaling: Why is everything so negative?

Current Opinion in Cell Biology

Volumn 10, Issue 2, 1998, Pages 182-187

  Brown, Jeffrey D ^a   Moon, Randall T ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA CATENIN; GLYCOPROTEIN;

ANIMAL CELL; CELL CULTURE; EMBRYO; EMBRYO DEVELOPMENT; GENE ACTIVATION; MOLECULAR EVOLUTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FAMILY; REVIEW; SIGNAL TRANSDUCTION;

EID: 0032054828     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0955-0674(98)80140-3     Document Type: Article

References (64)

1. Miller JR, Moon RT. Signal transduction through β-catenin and specification of cell fate during embryogenesis. Genes Dev. 10:1996;2527-2539.
2. Torres MA, Yang-Snyder JA, Purcell SM, DeMarais AA, McGrew LL, Moon RT. Activities of the Wnt-1 class of secreted signaling factors are antagonized by the Wnt-5a class and by a dominant negative cadherin in early Xenopus development. J Cell Biol. 133:1996;1123-1137.
3. Glinka A, Wu W, Onichtchouk D, Blumenstock C, Niehrs C. Head induction by simultaneous repression of BMP and Wnt signalling in Xenopus. of special interest Nature. 389:1997;517-519 Cerberus, a novel secreted protein expressed in the dorsal gastrula (Spemann's) organizer in Xenopus blocks Wnt-8 function. This study extends recent findings that Spemann's organizer is the source of multiple secreted antagonists of Wnt and BMP signaling.
4. Moon RT, Brown JD, Yang-Snyder JA, Miller JR. Structurally related receptors and antagonists compete for secreted Wnt ligands. Cell. 88:1997;725-728.
5. Szuts D, Freeman M, Bienz M. Antagonism between EGFR and Wingless signaling in the larval cuticle of Drosophila. Development. 124:1997;3209-3219.
6. Treisman JE, Luk A, Rubin GM, Heberlein U. eyelid antagonizes wingless signaling during Drosophila development and has homology to the Bright family of DNA-binding proteins. Genes Dev. 11:1997;1949-1962.
7. Yost C, Torres M, Miller JR, Huang E, Kimelman D, Moon RT. The axis-inducing activity, stability and subcellular distribution of β-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3. Genes Dev. 10:1996;1443-1454.
8. Rubinfeld B, Souza B, Albert I, Portiri E, Fiol C, Munemitsu S, Polakis P. Binding of GSK-3β to the APC - β-catenin complex and regulation of complex assembly. Science. 272:1996;1023-1026.
9. Aberle H, Bauer A, Stappert K, Kispert A, Kemler R. β-catenin is a target for the ubiquitin-proteasome pathway. EMBO J. 16:1997;3797-3804.
10. Parr BA, McMahon AP. Wnt genes and vertebrate development. Curr Opin Genet Dev. 4:1994;523-528.
11. Wang Y, Macke JP, Abella BS, Andreasson K, Worley P, Gilbert D, Copeland NG, Jenkins NA, Nathans J. A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled. J Biol Chem. 27:1996;4468-4476.
12. Bhanot P, Brink M, Samos CH, Hsieh J-C, Wang Y, Macke JP, Andrew D, Nathans J, Nusse R. A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature. 382:1996;225-230.
13. Yang-Snyder J, Miller JR, Brown JD, Lai CJ, Moon RT. A frizzled homolog functions in a vertebrate Wnt signaling pathway. Curr Biol. 6:1996;1302-1306.
14. He X, Saint-Jeannet J-P, Wang Y, Nathans J, Dawid I, Varmus H. A member of the frizzled protein family mediating axis induction by Wnt-5a. of special interest Science. 275:1997;1652-1654 Frizzled 5 is capable of transducing 'Wnt-1 like' signals in cooperation with Wnt-5a. This suggests that distinct Wnt signaling pathways can be activated by means of the same Wnt interacting with different members of the Frizzled family (see [51]).
15. Klingensmith J, Nusse R, Perrimon N. The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to the wingless signal. Genes Dev. 8:1994;118-130.
16. Willert K, Brink M, Wodarz A, Varmus H, Nusse R. Casein kinase 2 associates with and phosphorylates Dishevelled. of special interest EMBO J. 16:1997;3089-3096 Overexpression of Dishevelled in an imaginal disc cell line results in hyperphosphorylation of Dishevelled and accumulation of Armadillo. A kinase associated with immunoprecipitated Dishevelled was purified, microsequenced and was determined to be CKII (casien kinase II). Although CKII seems to phosphorylate Dishevelled upon overexpression of Frizzled-2 in the absence of Wingless, this phosphorylation is not sufficient to result in accumulation of Armadillo.
17. Yanagawa S, van Leeuwen F, Wodarz A, Klingensmith J, Nusse R. The dishevelled protein is modified by wingless signalling in Drosophila. Genes Dev. 9:1995;1087-1097.
18. Cook D, Fry MJ, Hughes K, Sumathipala R, Woodgett JR, Dale TC. Wingless inactivates glycogen synthase kinase-3 via an intracellular signalling pathway which involves a protein kinase C. EMBO J. 15:1996;4526-4536.
19. Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V, Roose J, Destreee O, Clevers H. XTcf-3 transcription factor mediates β-catenin-induced axis formation in Xenopus embryos. Cell. 86:1996;391-399.
20. Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W. Functional interaction of β-catenin with the transcription factor LEF-1. Nature. 382:1996;638-642.
21. Huber AH, Nelson WJ, Weis WI. Three-dimensional structure of the armadillo repeat region of β-catenin. of outstanding interest Cell. 90:1997;871-882 The structure of the arm repeat region of β-catenin suggests that the protein contains 12, not 13, repeats. The structure also reveals a basic groove in the repeat region that is likely responsible for interaction with acidic regions of LEF/TCF, APC and cadherin.
22. van de Wetering M, Cavallo R, Dooijes D, van Beest M, van Es J, Loureiro J, Ypma A, Hursh D, Jones T, Bejsovec A, et al. Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. of special interest Cell. 88:1997;789-799 A Drosophila TCF homolog was cloned and shown to be necessary for transduction of Armadillo signaling. A carboxy-terminal domain of Armadillo and β-catenin is shown to act as a transcriptional activator when bound to a minimal promoter. Interestingly, the authors identify a mutant of Armadillo that cannot associate with dTCF in two-hybrid assays but which still enters the nucleus, suggesting that this translocation occurs independently of association with dTCF.
23. Riese J, Yu X, Munnerlyn A, Eresh S, Hsu S-C, Grosschedl R, Bienz M. LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic. Cell. 88:1997;777-787.
24. Brannon M, Gomperts M, Sumoy L, Moon RT, Kimelman D. A β-catenin - XTCF-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus. of special interest Genes Dev. 11:1997;2359-2370 β-catenin responsiveness of a 0.8 kb fragment of the siamois promoter requires consensus LEF/TCF sites. Mutation of those sites results in loss of β-catenin responsiveness and an increase in basal transcription, suggesting that XTcf-3 may be bound to the promoter and repress transcription in the absence of β-catenin.
25. Cavallo R, Rubenstein D, Peifer M. Armadillo and dTCF: a marriage made in the nucleus. Curr Opin Genet Dev. 7:1997;459-466.
26. Nusse R. A versatile transcriptional effector of wingless signaling. Cell. 89:1997;321-323.
27. Orsulic S, Peifer M. Cell - cell signalling: wingless lands at last. Curr Biol. 6:1996;1363-1367.
28. Moon RT, Brown JD, Torres M. Wnts modulate cell fate and behavior during vertebrate development. Trends Genet. 13:1997;157-162.
29. 2+ signaling by Wnt-5a can be mimicked by stimulation of the PI cycle by activation of a serotonin receptor.
30. 2+ signaling by G-protein-linked P1 signaling and can synergize with Wnt-5a. This study confirms earlier suggestions that some Wnts may activate the PI cycle and places heterotrimeric G-proteins in this pathway.
31. Strutt DI, Weber U, Mlodzik M. The role of RhoA in tissue polarity and frizzled signalling. Nature. 387:1997;292-295.
32. Adler PA. The genetic control of tissue polarity in Drosophila. Bioessays. 14:1992;735-741.
33. Thorpe CJ, Schlesinger A, Carter JC, Bowerman B. Wnt signaling polarizes an early C. elegans blastomere to distinguish endoderm from mesoderm. Cell. 90:1997;695-705.
34. Rocheleau CE, Downs WD, Lin R, Wittmann C, Bei Y, Cha Y-H, Ali M, Priese JR, Mello CC. Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. of outstanding interest Cell. 90:1997;707-716 Several components of the Wnt signal transduction pathway were recovered in screens for excess muscle production in C. elegans. Other components were identified by homology with known Drosophila and vertebrate genes and were tested by 'RNA-mediated interference', a poorly understood but extremely powerful technique for specifically blocking gene function in C. elegans. The elegant combination of genetics, genomics and molecular biology available in this system are demonstrated. In contrast to other systems studied, the endogenous LEF/TCF homolog and Wnt signaling seem to have strictly antagonistic roles.
35. Thomsen GH. Antagonism within and around the organizer: BMP inhibitors in vertebrate body patterning. Trends Genet. 13:1997;209-211.
36. Hoang B, Moos M, Vukicevic S, Luyten FP. Primary structure and tissue distribution of FRZB, a novel protein related to Drosophila frizzled, suggest a role in skeletal and morphogenesis. J Biol Chem. 271:1996;26131-26137.
37. Lin K, Wang S, Julius MA, Kitajewski J, Moos M, Luyten FP. The cysteine-rich frizzled domain of frzb-1 is required and sufficient for modulation of Wnt signaling. of special interest Proc Natl Acad Sci USA. 94:1997;11196-11200 Deletion mutants of Frzb-1 were used to define the Wnt-binding domain of this antagonist. Although deletion of the domain homologous to Frizzled abrogates interaction with Wnt-1 and the ability of Frzb-1 to block Wnt-1 signaling, smaller deletions in that domain do not disrupt binding to Wnt-1 but do disrupt Wnt-1 antagonism. This study suggests that biochemical interactions of Frzb and Wnt do not necessarily imply inhibition of Wnt function.
38. Leyns L, Bouwmeester T, Kim S-H, Piccolo S, DeRobertis EM. Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer. of special interest Cell. 88:1997;747-756 Frzb-1, a secreted antagonist of Wnt signaling can bind Wnt-1 and block embryonic responses to Wnt-1 and Wnt-8 signaling. A domain of Frzb-1 is closely related to the extracellular ligand-binding domain of Frizzled receptors.
39. Shirozu M, Tada H, Tashiro K, Nakamura T, Lopez ND, Nazarea M, Hamada T, Sato T, Nakano T, Honjo T. Characterization of novel secreted and membrane proteins isolated by the signal sequence trap method. Genomics. 37:1996;273-280.
40. Pfeffer PL, De-Robertis EM, Izpisua-Belmonte JC. Crescent, a novel chick gene encoding a Frizzled-like cysteine-rich domain, is expressed in anterior regions during early embryogenesis. Int J Dev Biol. 41:1997;449-458.
41. Finch PW, He X, Kelley MJ, Uren A, Schaudies RP, Popescu NC, Rudikoff S, Aaronson SA, Varmus HE, Rubin JS. Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action. of special interest Proc Natl Acad Sci USA. 94:1997;6770-6775 FRP, a member of the Frzb family, was isolated and shown to inhibit the activity of Wnt-1, Wnt-8 and Wingless, but not Wnt-3a. This result demonstrates that Frzbs can discriminate between Wnts that have similar activities.
42. Mayr T, Deutsch U, Kuhl M, Drexler HCA, Lottspeich F, Deutzmann R, Wedlich D, Risau W. Fritz: a secreted frizzled-related protein that inhibits Wnt activity. Mech Dev. 63:1997;109-125.
43. Salic AN, Kroll KL, Evans LM, Kirschner MW. Sizzled: a secreted Xwnt8 antagonist expressed in the ventral marginal zone of Xenopus embryos. Development. 124:1997;4739-4748.
44. Rattner A, Hsieh J-C, Smallwood PM, Gilbert DJ, Copeland NG, Jenkins NA, Nathans J. A family of secreted proteins contains homology to the cysteine-rich ligand-binding domain of frizzled receptors. of special interest Proc Natl Acad Sci USA. 94:1997;2859-2863 Four sFRP genes, members of the Frzb family, are cloned from mouse, revealing that these secreted Wnt antagonists comprise a multi-gene family.
45. Wang S, Krinks M, Lin K, Luyten FP, Moos M. Frzb, a secreted protein expressed in the Spemann organizer, binds and inhibits Wnt-8. of outstanding interest Cell. 88:1997;757-766 Xenopus Frzb-1 was cloned and shown to inhibit Wnt signaling and interact with Wnt proteins by coimmunoprecipitation.
46. Wong GT, Gavin BJ, McMahon AP. Differential transformation of mammary epithelial cells by Wnt genes. Mol Cel Biol. 14:1994;6278-6286.
47. Du SJ, Purcell SM, Christian JL, McGrew LL, Moon RT. Identification of distinct classes and functional domains of Wnts through expression of wild-type and chimeric proteins in Xenopus embryos. Mol Cell Biol. 15:1995;2625-2634.
48. Wang S, Krinks M, Moos M. Frzb-1, an antagonist of Wnt-1 and Wnt-8, does not block signaling by Wnts-3a, -5a, or -11. of special interest Biochem Biophys Res Commun. 236:1997;502-504 Frzb-1 does not antagonize 'Wnt-5a class' function and discriminates between different Wnts in the 'Wnt-1 class'. Signaling by Wnt-1 and Wnt-8 are blocked, but Wnt-3a activity is not significantly inhibited.
49. Bouwmeester T, Kim S-H, Sasai Y, Lu B, DeRobertis EM. Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann's ogranizer. Nature. 382:1996;595-601.
50. Christian J, Moon RT. Interactions between Xwnt-8 and Spemann organizer signaling pathways generate dorsoventral pattern in the embryonic mesoderm of Xenopus. Genes Dev. 7:1993;13-28.
51. Larabell CA, Torres M, Rowning BA, Yost C, Miller JR, Wu M, Kimelman D, Moon RT. Establishment of the dorso-ventral axis in Xenopus embryos is presaged by early asymmetrics in β-catenin that are modulated by the Wnt signaling pathway. of special interest J Cell Biol. 136:1997;1123-1136 Before the onset of zygotic transcription in Xenopus embryos, Wnt-5a can block embryonic responses to Wnt-8 (see [2]). After the onset of zygotic transcription, overexpression of Wnt-5a results in the stabilization of β-catenin, suggesting that distinct pathways can be activated by a single Wnt ligand.
52. Miller JR, Moon RT. Analysis of the signaling activities of localization mutants of β-catenin during axis specification in Xenopus. of special interest J Cell Biol. 139:1997;229-243 Overexpression of a transmembrane-tethered form of β-catenin results in activation of the Wnt pathway in Xenopus embryos. This activity is probably the result of overloading the β-catenin degradation pathway which allows the stabilization of the endogenous free β-catenin. This study helps to clarify the mechanism of signaling activity of β-catenin which cannot itself translocate to the nucleus.
53. Pai LM, Orsulic S, Bejsovec A, Peifer M. Negative regulation of Armadillo, a Wingless effector in Drosophila. Development. 124:1997;2255-2266.
54. Hayashi S, Rubinfeld B, Souza B, Polakis P, Wieschaus E, Levine AJ. A Drosophila homolog of the tumor suppressor gene adenomatous polyposis coli down-regulates β-catenin but its zygotic expression is not essential for the regulation of Armadillo. Proc Natl Acad Sci USA. 94:1997;242-247.
55. Moon RT, Miller JR. The APC tumor suppressor protein in development and cancer. Trends Genet. 13:1997;256-258.
56. Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek TJ, Perry WL, Lee JJ, Tilghman SM, Gumbiner BM, Constantini F. The mouse Fused locus encodes axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation. of special interest Cell. 90:1997;181-192 Axin seems to be a negative regulator of Wnt signaling, and deletion of an RGS-like domain results in a 'dominant negative' Axin that activates Wnt signaling. Although the mechanism of Axin action is unknown, presence of the RGS domain may suggest the involvement of heterotrimeric G-proteins.
57. Carnac G, Kodjabachian L, Gurdon JB, Lemaire P. The homeobox gene siamois is a target of the Wnt dorsalisation pathway and triggers organiser activity in the absence of mesoderm. Development. 122:1996;3055-3065.
58. Brannon M, Kimelman D. Activation of siamois by the Wnt pathway. Dev Biol. 180:1996;344-347.
59. Koelle MR. A new family of G-protein regulators-the RGS proteins. Curr Opin Cell Biol. 9:1997;143-147.
60. Huber O, Korn R, McLaughlin J, Ohsugi M, Gerrmann BG, Kemler R. Nuclear localization of β-catenin by interaction with transcription factor LEF-1. Mech Dev. 59:1996;3-10.
61. Brunner E, Peter O, Schweizer L, Basler K. pangolin encodes a LEF-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila. of outstanding interest Nature. 385:1997;829-833 A screen for supressors of the rough-eye phenotype caused by ectopic Wingless expression resulted in the isolation of mutants in armadillo and pangolin, a LEF/TCF homolog. Two missense mutations in pangolin map to the amino terminus of the protein - the region known to interact with Armadillo. Loss-of-function alleles of pangolin result in segment polarity phenotypes which are insensitive to Armadillo overexpression and suggest that Pangolin is absolutely required for Wingless signaling.
62. Klymkowsky MW. Minireviews, minidogmas and mythinformation. BioEssays. 19:1997;537-539.
63. Han M. Gut reaction to Wnt signaling in worms. Cell. 90:1997;581-584.
64. Gilinka A, Wu W, Delius H, Monaghan AP, Blumenstock C, Niehrs C. Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature. 391:1998;357-362.