PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling - PubMed (original) (raw)

PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling

T Q Sun et al. Nat Cell Biol. 2001 Jul.

Abstract

Wnt signalling regulates beta-catenin-dependent developmental processes through the Dishevelled protein (Dsh). Dsh regulates two distinct pathways, one mediated by beta-catenin and the other by Jun kinase (JNK). We have purified a Dsh-associated kinase from Drosophila that encodes a homologue of Caenorhabditis elegans PAR-1, a known determinant of polarity during asymmetric cell divisions. Treating cells with Wnt increases endogenous PAR-1 activity coincident with Dsh phosphorylation. PAR-1 potentiates Wnt activation of the beta-catenin pathway but blocks the JNK pathway. Suppressing endogenous PAR-1 function inhibits Wnt signalling through beta-catenin in mammalian cells, and Xenopus and Drosophila embryos. PAR-1 seems to be a positive regulator of the beta-catenin pathway and an inhibitor of the JNK pathway. These findings show that PAR-1, a regulator of polarity, is also a modulator of Wnt-beta-catenin signalling, indicating a link between two important developmental pathways.

PubMed Disclaimer

Comment in

• PAR-1 helps Wnt to get rid of JNK.
  Depraetere V. Depraetere V. Nat Cell Biol. 2001 Jul;3(7):E158. doi: 10.1038/35083107. Nat Cell Biol. 2001. PMID: 11433308 No abstract available.

Similar articles

• New steps in the Wnt/beta-catenin signal transduction pathway.
  Sakanaka C, Sun TQ, Williams LT. Sakanaka C, et al. Recent Prog Horm Res. 2000;55:225-36. Recent Prog Horm Res. 2000. PMID: 11036939 Review.
• PAR-1 helps Wnt to get rid of JNK.
  Depraetere V. Depraetere V. Nat Cell Biol. 2001 Jul;3(7):E158. doi: 10.1038/35083107. Nat Cell Biol. 2001. PMID: 11433308 No abstract available.
• Casein kinase Iepsilon modulates the signaling specificities of dishevelled.
  Cong F, Schweizer L, Varmus H. Cong F, et al. Mol Cell Biol. 2004 Mar;24(5):2000-11. doi: 10.1128/MCB.24.5.2000-2011.2004. Mol Cell Biol. 2004. PMID: 14966280 Free PMC article.
• The C-terminal cytoplasmic Lys-thr-X-X-X-Trp motif in frizzled receptors mediates Wnt/beta-catenin signalling.
  Umbhauer M, Djiane A, Goisset C, Penzo-Méndez A, Riou JF, Boucaut JC, Shi DL. Umbhauer M, et al. EMBO J. 2000 Sep 15;19(18):4944-54. doi: 10.1093/emboj/19.18.4944. EMBO J. 2000. PMID: 10990458 Free PMC article.
• TCF: Lady Justice casting the final verdict on the outcome of Wnt signalling.
  Brantjes H, Barker N, van Es J, Clevers H. Brantjes H, et al. Biol Chem. 2002 Feb;383(2):255-61. doi: 10.1515/BC.2002.027. Biol Chem. 2002. PMID: 11934263 Review.

Cited by

• A review of the evidence for the canonical Wnt pathway in autism spectrum disorders.
  Kalkman HO. Kalkman HO. Mol Autism. 2012 Oct 19;3(1):10. doi: 10.1186/2040-2392-3-10. Mol Autism. 2012. PMID: 23083465 Free PMC article.
• Signaling crosstalk between TGFβ and Dishevelled/Par1b.
  Mamidi A, Inui M, Manfrin A, Soligo S, Enzo E, Aragona M, Cordenonsi M, Wessely O, Dupont S, Piccolo S. Mamidi A, et al. Cell Death Differ. 2012 Oct;19(10):1689-97. doi: 10.1038/cdd.2012.50. Epub 2012 May 11. Cell Death Differ. 2012. PMID: 22576663 Free PMC article.
• The N and C termini of ZO-1 are surrounded by distinct proteins and functional protein networks.
  Van Itallie CM, Aponte A, Tietgens AJ, Gucek M, Fredriksson K, Anderson JM. Van Itallie CM, et al. J Biol Chem. 2013 May 10;288(19):13775-88. doi: 10.1074/jbc.M113.466193. Epub 2013 Apr 3. J Biol Chem. 2013. PMID: 23553632 Free PMC article.
• Loss of Cell Adhesion Increases Tumorigenic Potential of Polarity Deficient Scribble Mutant Cells.
  Waghmare I, Kango-Singh M. Waghmare I, et al. PLoS One. 2016 Jun 21;11(6):e0158081. doi: 10.1371/journal.pone.0158081. eCollection 2016. PLoS One. 2016. PMID: 27327956 Free PMC article.
• Wnt proteins induce dishevelled phosphorylation via an LRP5/6- independent mechanism, irrespective of their ability to stabilize beta-catenin.
  González-Sancho JM, Brennan KR, Castelo-Soccio LA, Brown AM. González-Sancho JM, et al. Mol Cell Biol. 2004 Jun;24(11):4757-68. doi: 10.1128/MCB.24.11.4757-4768.2004. Mol Cell Biol. 2004. PMID: 15143170 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • FlyBase
  • GlyGen glycoinformatics resource

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal