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GSK-3 / WNT SIGNALING
Wnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, in many different species and organs. There are at least three different Wnt pathways: the canonical pathway, the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway.
In the canonical Wnt pathway, the major effect of Wnt ligand binding to its receptor is the stabilization of cytoplasmic beta-catenin through inhibition of the bea-catenin degradation complex. Beta-catenin is then free to enter the nucleus and activate Wnt-regulated genes through its interaction with TCF (T-cell factor) family transcription factors and concomitant recruitment of coactivators.
Planar cell polarity (PCP) signaling leads to the activation of the small GTPases RHOA (RAS homologue gene-family member A) and RAC1, which activate the stress kinase JNK (Jun N-terminal kinase) and ROCK (RHO-associated coiled-coil-containing protein kinase 1) and leads to remodelling of the cytoskeleton and changes in cell adhesion and motility.
WNT-Ca2+ signalling is mediated through G proteins and phospholipases and leads to transient increases in cytoplasmic free calcium that subsequently activate the kinase PKC (protein kinase C) and CAMKII (calcium calmodulin mediated kinase II) and the phosphatase calcineurin.
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FREE REVIEW ARTICLES
- Wnt signalling pathway in the serrated neoplastic pathway of the colorectum: possible roles and epigenetic regulatory mechanisms., Xiangsheng Fu, Li Li, and Yan Peng. J. Clin. Pathol., Aug 2012; 65: 675 - 679.
- Wnt Signaling and Aging-Related Heart Disorders., Atsuhiko T. Naito, Ichiro Shiojima, and Issei Komuro. Circ. Res., Nov 2010; 107: 1295 – 1303.
- Role of WNT signalling in the determination of human mesenchymal stem cells into preadipocytes, Matthias Laudes. J. Mol. Endocrinol., Mar 2011; 46: R65 - R72.
- Phospholipase D Meets Wnt Signaling: A New Target for Cancer Therapy., Dong Woo Kang, Kang-Yell Choi, and Do Sik Min. Cancer Res., Jan 2011; 71: 293 - 297.
- Inhibition of GSK3 by Wnt signalling – two contrasting models. , Ciara Metcalfe and Mariann Bienz. J. Cell Sci., Nov 2011; 124: 3537 - 3544.
- Maintaining embryonic stem cell pluripotency with Wnt signaling. , Sergei Y. Sokol. Development, Oct 2011; 138: 4341 - 4350.
- Phosphoinositide 3-kinase signaling in the vertebrate retina. , Raju V. S. Rajala. J. Lipid Res., Jan 2010; 51: 4 - 22.
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