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PMID: 17928543 Published · ppublish English Journal Article Review

Phospho-regulation of Beta-catenin adhesion and signaling functions.

Physiology (Bethesda, Md.) ·Vol. 22 ·2007-10-00 ·Pages 303-9

Daugherty RL, Gottardi CJ

Abstract

Beta-catenin plays a critical structural role in cadherin-based adhesions and is also an essential co-activator of Wnt-mediated gene expression. The degree to which beta-catenin participates in these two functions is dictated by the availability of beta-catenin binding partners, and an emerging theme is that these binding interactions are regulated by phosphorylation. Inputs from various cell-signaling events can therefore impact beta-catenin function, which may be necessary for the finely tuned adhesive and signaling responses required for tissue morphogenesis.

MeSH Terms
Animals Cadherins/chemistry,metabolism Cell Adhesion/physiology DNA-Binding Proteins/chemistry,metabolism Gene Expression Regulation Humans Phosphorylation Protein Binding Protein Interaction Domains and Motifs/physiology Signal Transduction Trans-Activators/chemistry,metabolism Wnt Proteins/chemistry,genetics,metabolism beta Catenin/chemistry,genetics,metabolism
Chemicals
Cadherins DNA-Binding Proteins Trans-Activators Wnt Proteins beta Catenin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Daugherty Rebecca Leadem
The Integrated Graduate Program in the Life Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. c-gottardi@northwestern.edu
Gottardi Cara J
References (89)
89 references, click to expand
  1. Axin-dependent phosphorylation of the adenomatous polyposis coli protein mediated by casein kinase 1epsilon.
    J Biol Chem. 2001 Oct 19;276(42):39037-45 PMID: 11487578
  2. p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho.
    Cell. 2006 Dec 1;127(5):1027-39 PMID: 17129786
  3. A core function for p120-catenin in cadherin turnover.
    J Cell Biol. 2003 Nov 10;163(3):525-34 PMID: 14610055
  4. Parafibromin/Hyrax activates Wnt/Wg target gene transcription by direct association with beta-catenin/Armadillo.
    Cell. 2006 Apr 21;125(2):327-41 PMID: 16630820
  5. Mechanism of homophilic cadherin adhesion.
    Curr Opin Cell Biol. 2000 Oct;12(5):587-92 PMID: 10978894
  6. The tuberin-hamartin complex negatively regulates beta-catenin signaling activity.
    J Biol Chem. 2003 Feb 21;278(8):5947-51 PMID: 12511557
  7. Apc tumor suppressor gene is the "zonation-keeper" of mouse liver.
    Dev Cell. 2006 Jun;10(6):759-70 PMID: 16740478
  8. Molecular analysis of the armadillo locus: uniformly distributed transcripts and a protein with novel internal repeats are associated with a Drosophila segment polarity gene.
    Genes Dev. 1989 Jan;3(1):96-113 PMID: 2707602
  9. Beta-catenin N- and C-terminal tails modulate the coordinated binding of adherens junction proteins to beta-catenin.
    J Biol Chem. 2002 Aug 30;277(35):31541-50 PMID: 12077140
  10. Involvement of Src family kinases in N-cadherin phosphorylation and beta-catenin dissociation during transendothelial migration of melanoma cells.
    Mol Biol Cell. 2006 Mar;17(3):1261-72 PMID: 16371504
  11. Pygopus and legless provide essential transcriptional coactivator functions to armadillo/beta-catenin.
    Curr Biol. 2005 Jul 12;15(13):1207-11 PMID: 16005293
  12. shotgun encodes Drosophila E-cadherin and is preferentially required during cell rearrangement in the neurectoderm and other morphogenetically active epithelia.
    Genes Dev. 1996 Mar 15;10(6):672-85 PMID: 8598295
  13. Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex.
    Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1182-7 PMID: 11818547
  14. Wnt/beta-catenin signaling in development and disease.
    Cell. 2006 Nov 3;127(3):469-80 PMID: 17081971
  15. Wingless-independent association of Pygopus with dTCF target genes.
    Curr Biol. 2007 Mar 20;17(6):556-61 PMID: 17320388
  16. RanBP3 enhances nuclear export of active (beta)-catenin independently of CRM1.
    J Cell Biol. 2005 Dec 5;171(5):785-97 PMID: 16314428
  17. Essential role of BCL9-2 in the switch between beta-catenin's adhesive and transcriptional functions.
    Genes Dev. 2004 Sep 15;18(18):2225-30 PMID: 15371335
  18. Protein-kinase-C-mediated beta-catenin phosphorylation negatively regulates the Wnt/beta-catenin pathway.
    J Cell Sci. 2006 Nov 15;119(Pt 22):4702-9 PMID: 17093267
  19. In situ phosphorylation of immobilized receptors on biosensor surfaces: application to E-cadherin/beta-catenin interactions.
    Anal Biochem. 2006 Oct 15;357(2):277-88 PMID: 16945320
  20. Distinct molecular forms of beta-catenin are targeted to adhesive or transcriptional complexes.
    J Cell Biol. 2004 Oct 25;167(2):339-49 PMID: 15492040
  21. Cell adhesion: separation of p120's powers?
    Curr Biol. 2007 Jan 9;17(1):R24-7 PMID: 17208174
  22. The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes.
    Genes Dev. 2006 Mar 1;20(5):586-600 PMID: 16510874
  23. Overexpression of cadherins and underexpression of beta-catenin inhibit dorsal mesoderm induction in early Xenopus embryos.
    Cell. 1994 Dec 2;79(5):791-803 PMID: 7528101
  24. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity.
    EMBO J. 2000 Nov 15;19(22):6121-30 PMID: 11080158
  25. Casein kinase II phosphorylation of E-cadherin increases E-cadherin/beta-catenin interaction and strengthens cell-cell adhesion.
    J Biol Chem. 2000 Feb 18;275(7):5090-5 PMID: 10671552
  26. Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts.
    Mol Cell Biol. 2007 May;27(10):3804-16 PMID: 17353278
  27. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells.
    Cell. 2002 Oct 18;111(2):241-50 PMID: 12408868
  28. Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction.
    Nature. 2005 Dec 8;438(7069):867-72 PMID: 16341016
  29. Regulation of cadherin-mediated adhesion in morphogenesis.
    Nat Rev Mol Cell Biol. 2005 Aug;6(8):622-34 PMID: 16025097
  30. Physiological regulation of [beta]-catenin stability by Tcf3 and CK1epsilon.
    J Cell Biol. 2001 Sep 3;154(5):983-93 PMID: 11524435
  31. Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase stabilizes beta-catenin through inhibition of its ubiquitination.
    Mol Cell Biol. 2005 Oct;25(20):9063-72 PMID: 16199882
  32. Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated regulation of LEF-1.
    EMBO J. 1999 Aug 2;18(15):4233-40 PMID: 10428961
  33. Cell-adhesion molecule uvomorulin is localized in the intermediate junctions of adult intestinal epithelial cells.
    J Cell Biol. 1985 Jan;100(1):327-32 PMID: 3880756
  34. Alpha 1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex.
    Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8813-7 PMID: 7568023
  35. Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase.
    J Biol Chem. 2006 Apr 14;281(15):9971-6 PMID: 16476742
  36. Armadillo is required for adherens junction assembly, cell polarity, and morphogenesis during Drosophila embryogenesis.
    J Cell Biol. 1996 Jul;134(1):133-48 PMID: 8698810
  37. Cinderella no longer: alpha-catenin steps out of cadherin's shadow.
    J Cell Sci. 2006 Nov 15;119(Pt 22):4599-605 PMID: 17093264
  38. Thermodynamics of beta-catenin-ligand interactions: the roles of the N- and C-terminal tails in modulating binding affinity.
    J Biol Chem. 2006 Jan 13;281(2):1027-38 PMID: 16293619
  39. Binding to cadherins antagonizes the signaling activity of beta-catenin during axis formation in Xenopus.
    J Cell Biol. 1996 Mar;132(6):1105-14 PMID: 8601588
  40. Armadillo nuclear import is regulated by cytoplasmic anchor Axin and nuclear anchor dTCF/Pan.
    Development. 2001 Jun;128(11):2107-17 PMID: 11493532
  41. Regulation of S33/S37 phosphorylated beta-catenin in normal and transformed cells.
    J Cell Sci. 2002 Jul 1;115(Pt 13):2771-80 PMID: 12077367
  42. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly.
    Science. 1996 May 17;272(5264):1023-6 PMID: 8638126
  43. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism.
    Cell. 2002 Mar 22;108(6):837-47 PMID: 11955436
  44. Wnt signaling: complexity at the surface.
    J Cell Sci. 2006 Feb 1;119(Pt 3):395-402 PMID: 16443747
  45. Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of beta-catenin.
    Curr Biol. 1998 Feb 12;8(4):181-90 PMID: 9501980
  46. Alpha-catenin is a molecular switch that binds E-cadherin-beta-catenin and regulates actin-filament assembly.
    Cell. 2005 Dec 2;123(5):903-15 PMID: 16325583
  47. Crystal structure of a beta-catenin/axin complex suggests a mechanism for the beta-catenin destruction complex.
    Genes Dev. 2003 Nov 15;17(22):2753-64 PMID: 14600025
  48. Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation.
    Mol Cell. 2004 Aug 27;15(4):511-21 PMID: 15327768
  49. Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex.
    EMBO J. 2007 Mar 21;26(6):1511-21 PMID: 17318175
  50. Armadillo repeat proteins: beyond the animal kingdom.
    Trends Cell Biol. 2003 Sep;13(9):463-71 PMID: 12946625
  51. The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3.
    Genes Dev. 1996 Jun 15;10(12):1443-54 PMID: 8666229
  52. Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex.
    EMBO J. 2003 Feb 3;22(3):494-501 PMID: 12554650
  53. Notch modulates Wnt signalling by associating with Armadillo/beta-catenin and regulating its transcriptional activity.
    Development. 2005 Apr;132(8):1819-30 PMID: 15772135
  54. A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression.
    Biochem Biophys Res Commun. 1999 Dec 9;266(1):28-35 PMID: 10581160
  55. Functional characterization of multiple transactivating elements in beta-catenin, some of which interact with the TATA-binding protein in vitro.
    J Biol Chem. 1999 Jun 18;274(25):18017-25 PMID: 10364252
  56. Wnt signaling: is the party in the nucleus?
    Genes Dev. 2006 Jun 1;20(11):1394-404 PMID: 16751178
  57. The p300/CBP acetyltransferases function as transcriptional coactivators of beta-catenin in vertebrates.
    EMBO J. 2000 Apr 17;19(8):1839-50 PMID: 10775268
  58. Depolarization drives beta-Catenin into neuronal spines promoting changes in synaptic structure and function.
    Neuron. 2002 Jul 3;35(1):91-105 PMID: 12123611
  59. Molecular cloning of human E-cadherin suggests a novel subdivision of the cadherin superfamily.
    Biochem Biophys Res Commun. 1994 May 16;200(3):1754-61 PMID: 8185635
  60. Nucleo-cytoplasmic distribution of beta-catenin is regulated by retention.
    J Cell Sci. 2006 Apr 1;119(Pt 7):1453-63 PMID: 16554443
  61. The chromatin remodelling factor Brg-1 interacts with beta-catenin to promote target gene activation.
    EMBO J. 2001 Sep 3;20(17):4935-43 PMID: 11532957
  62. A short core region of E-cadherin is essential for catenin binding and is highly phosphorylated.
    Cell Adhes Commun. 1994 Aug;2(4):319-27 PMID: 7820535
  63. Deconstructing the cadherin-catenin-actin complex.
    Cell. 2005 Dec 2;123(5):889-901 PMID: 16325582
  64. Structure-function analysis of Frizzleds.
    Cell Signal. 2006 Jul;18(7):934-41 PMID: 16480852
  65. Wnt signaling and cancer.
    Genes Dev. 2000 Aug 1;14(15):1837-51 PMID: 10921899
  66. Three-dimensional structure of the armadillo repeat region of beta-catenin.
    Cell. 1997 Sep 5;90(5):871-82 PMID: 9298899
  67. A mode of regulation of beta-catenin signaling activity in Xenopus embryos independent of its levels.
    Dev Biol. 2000 Jul 15;223(2):441-8 PMID: 10882528
  68. Functional interaction of beta-catenin with the transcription factor LEF-1.
    Nature. 1996 Aug 15;382(6592):638-42 PMID: 8757136
  69. The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell.
    Curr Biol. 1999 Feb 25;9(4):207-10 PMID: 10074433
  70. Wnt signaling controls the phosphorylation status of beta-catenin.
    J Biol Chem. 2002 May 17;277(20):17901-5 PMID: 11834740
  71. Axin: a master scaffold for multiple signaling pathways.
    Neurosignals. 2004 May-Jun;13(3):99-113 PMID: 15067197
  72. Functional correlates of mutations in beta-catenin exon 3 phosphorylation sites.
    J Biol Chem. 2003 Aug 22;278(34):31781-9 PMID: 12799363
  73. P68 RNA helicase mediates PDGF-induced epithelial mesenchymal transition by displacing Axin from beta-catenin.
    Cell. 2006 Oct 6;127(1):139-55 PMID: 17018282
  74. Wnt/beta-catenin/CBP signaling maintains long-term murine embryonic stem cell pluripotency.
    Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5668-73 PMID: 17372190
  75. Cdc42 controls progenitor cell differentiation and beta-catenin turnover in skin.
    Genes Dev. 2006 Mar 1;20(5):571-85 PMID: 16510873
  76. CK2 controls the recruitment of Wnt regulators to target genes in vivo.
    Curr Biol. 2006 Nov 21;16(22):2239-44 PMID: 17113388
  77. Cyclin-dependent kinase 2 regulates the interaction of Axin with beta-catenin.
    Biochem Biophys Res Commun. 2004 Apr 30;317(2):478-83 PMID: 15063782
  78. Regulation of E-cadherin/Catenin association by tyrosine phosphorylation.
    J Biol Chem. 1999 Dec 17;274(51):36734-40 PMID: 10593980
  79. Cellular levels of p120 catenin function as a set point for cadherin expression levels in microvascular endothelial cells.
    J Cell Biol. 2003 Nov 10;163(3):535-45 PMID: 14610056
  80. Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex.
    Genes Dev. 1999 Jul 15;13(14):1768-73 PMID: 10421629
  81. The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin.
    Cell. 2001 May 4;105(3):391-402 PMID: 11348595
  82. Wnt signals are transmitted through N-terminally dephosphorylated beta-catenin.
    EMBO Rep. 2002 Jan;3(1):63-8 PMID: 11751573
  83. The juxtamembrane region of the cadherin cytoplasmic tail supports lateral clustering, adhesive strengthening, and interaction with p120ctn.
    J Cell Biol. 1998 May 4;141(3):779-89 PMID: 9566976
  84. Coupling assembly of the E-cadherin/beta-catenin complex to efficient endoplasmic reticulum exit and basal-lateral membrane targeting of E-cadherin in polarized MDCK cells.
    J Cell Biol. 1999 Feb 22;144(4):687-99 PMID: 10037790
  85. A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation.
    Nature. 2005 Dec 8;438(7069):873-7 PMID: 16341017
  86. Modulation of beta-catenin by cyclin-dependent kinase 6 in Wnt-stimulated cells.
    Eur J Cell Biol. 2007 Feb;86(2):111-23 PMID: 17208333
  87. Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity.
    J Biol Chem. 2007 Apr 13;282(15):11221-9 PMID: 17287208
  88. The cadherin cytoplasmic domain is unstructured in the absence of beta-catenin. A possible mechanism for regulating cadherin turnover.
    J Biol Chem. 2001 Apr 13;276(15):12301-9 PMID: 11121423
  89. Translocation of beta-catenin into the nucleus independent of interactions with FG-rich nucleoporins.
    Exp Cell Res. 2003 Nov 1;290(2):447-56 PMID: 14568002
Article Info
Journal
Physiology (Bethesda, Md.)
Abbr.
Physiology (Bethesda)
ISSN
1548-9213
DOI
10.1152/physiol.00020.2007
Email
c-gottardi@northwestern.edu
Published
2007-10-00
Pages
303-9
Language
English
Region
United States
NLM ID
101208185
PMCID
PMC2276853
Subset
IM
Grants
NIGMS NIH HHS · R01 GM076561 · United States
NIGMS NIH HHS · R01 GM076561-03 · United States
External Links
PubMed source DOI: 10.1152/physiol.00020.2007 PMC Full Text View journal details
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