Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway
- PMID: 11336703
- DOI: 10.1016/s1097-2765(01)00224-6
Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway
Abstract
To understand how the Wnt coreceptor LRP-5 is involved in transducing the canonical Wnt signals, we identified Axin as a protein that interacts with the intracellular domain of LRP-5. LRP-5, when expressed in fibroblast cells, showed no effect on the canonical Wnt signaling pathway by itself, but acted synergistically with Wnt. In contrast, LRP-5 mutants lacking the extracellular domain functioned as constitutively active forms that bind Axin and that induce LEF-1 activation by destabilizing Axin and stabilizing beta-catenin. Addition of Wnt caused the translocation of Axin to the membrane and enhanced the interaction between Axin and LRP-5. In addition, the LRP-5 sequences involved in interactions with Axin are required for LEF-1 activation. Thus, we conclude that the binding of Axin to LRP-5 is an important part of the Wnt signal transduction pathway.
Similar articles
-
Second cysteine-rich domain of Dickkopf-2 activates canonical Wnt signaling pathway via LRP-6 independently of dishevelled.J Biol Chem. 2002 Feb 22;277(8):5977-81. doi: 10.1074/jbc.M111131200. Epub 2001 Dec 12. J Biol Chem. 2002. PMID: 11742004
-
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. doi: 10.1093/emboj/18.15.4233. EMBO J. 1999. PMID: 10428961 Free PMC article.
-
Interaction between LRP5 and Frat1 mediates the activation of the Wnt canonical pathway.J Biol Chem. 2005 Apr 8;280(14):13616-23. doi: 10.1074/jbc.M411999200. Epub 2005 Feb 7. J Biol Chem. 2005. PMID: 15699046
-
Roles of Axin in the Wnt signalling pathway.Cell Signal. 1999 Nov;11(11):777-88. doi: 10.1016/s0898-6568(99)00054-6. Cell Signal. 1999. PMID: 10617280 Review.
-
New steps in the Wnt/beta-catenin signal transduction pathway.Recent Prog Horm Res. 2000;55:225-36. Recent Prog Horm Res. 2000. PMID: 11036939 Review.
Cited by
-
Membrane bound GSK-3 activates Wnt signaling through disheveled and arrow.PLoS One. 2015 Apr 7;10(4):e0121879. doi: 10.1371/journal.pone.0121879. eCollection 2015. PLoS One. 2015. PMID: 25848770 Free PMC article.
-
SerpinB3: A Multifaceted Player in Health and Disease-Review and Future Perspectives.Cancers (Basel). 2024 Jul 18;16(14):2579. doi: 10.3390/cancers16142579. Cancers (Basel). 2024. PMID: 39061218 Free PMC article. Review.
-
The Wnt signaling cascade in the pathogenesis of osteoarthritis and related promising treatment strategies.Front Physiol. 2022 Sep 2;13:954454. doi: 10.3389/fphys.2022.954454. eCollection 2022. Front Physiol. 2022. PMID: 36117702 Free PMC article. Review.
-
Why Is Wnt/β-Catenin Not Yet Targeted in Routine Cancer Care?Pharmaceuticals (Basel). 2024 Jul 16;17(7):949. doi: 10.3390/ph17070949. Pharmaceuticals (Basel). 2024. PMID: 39065798 Free PMC article. Review.
-
WNT Signaling in Melanoma.Int J Mol Sci. 2020 Jul 9;21(14):4852. doi: 10.3390/ijms21144852. Int J Mol Sci. 2020. PMID: 32659938 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous