Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3–independent β-catenin degradation
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Open Access
- 1 September 2003
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 162 (5) , 899-908
- https://doi.org/10.1083/jcb.200303158
Abstract
Wnts are secreted signaling molecules that can transduce their signals through several different pathways. Wnt-5a is considered a noncanonical Wnt as it does not signal by stabilizing β-catenin in many biological systems. We have uncovered a new noncanonical pathway through which Wnt-5a antagonizes the canonical Wnt pathway by promoting the degradation of β-catenin. This pathway is Siah2 and APC dependent, but GSK-3 and β-TrCP independent. Furthermore, we provide evidence that Wnt-5a also acts in vivo to promote β-catenin degradation in regulating mammalian limb development and possibly in suppressing tumor formation.Keywords
This publication has 62 references indexed in Scilit:
- Wnt-5/pipetail functions in vertebrate axis formation as a negative regulator of Wnt/β-catenin activityThe Journal of cell biology, 2003
- Armadillo/β-catenin signals in the nucleus – proof beyond a reasonable doubt?Nature Cell Biology, 2003
- The Promise and Perils of Wnt Signaling Through β-CateninScience, 2002
- The Wnt/calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryosNature, 2002
- NFAT SignalingCell, 2002
- Wnt Signaling in Oncogenesis and Embryogenesis--a Look Outside the NucleusScience, 2000
- MECHANISMS OF WNT SIGNALING IN DEVELOPMENTAnnual Review of Cell and Developmental Biology, 1998
- Sequential Progression of the Differentiation Program by Bone Morphogenetic Protein-2 in Chondrogenic Cell Line ATDC5Experimental Cell Research, 1998
- Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC −/− Colon CarcinomaScience, 1997
- The influence of epithelia on cartilage and loose connective tissue formation by limb mesenchyme culturesDevelopmental Biology, 1981