Wnt/-catenin signaling pathway

Wnt/-catenin signaling pathway. Wnts are secreted glycoproteins that bind to their cognate receptors, Frizzleds. Frizzleds belong to a family of heptahelical, G-protein-coupled receptors that bind specific Wnts and transduce the signal to downstream signalling pathways. Under basal conditions, cellular -catenin is phosphorylated by a Serine/Threonine kinase, Glycogen Synthase Kinase-3 (GSK3) in a complex along with Axin, adenomatous polyposis coli (APC) and other elements. The phosphorylated -catenin is constantly subjected to a proteasome-mediated degradation. Wnt-activated Frizzled (with its co-receptor low-density lipoprotein-related receptor protein-6 (LRP6)) activate the downstream signalling components including G-proteins, Go and Gq, and a phosphoprotein, Dishevelled. Dishevelleds, by an unclear mechanism, lead to reduced GSK3 kinase activity. Suppression of GSK3 activity leads to elevation of cytosolic and nuclear -catenin levels. Elevated nuclear -catenin levels activates the lymphoid-enhancer factor/T-cell factor (Lef/Tcf)-sensitive transcription, turning on the genes that are necessary for development. Note: for complete list of proteins involved in Wnt signalling, refer to the Wnt home page (http://www.stanford.edu/~rnusse/wntwindow.html).

Publication

Mitogen-activated protein kinases and Wnt/β-catenin signaling. (2009) Rama Kamesh Bikkavilli, et al. Commun Integr Biol. 2009 Jan-Feb;2(1):46-49. Figure: F2. All organisms Drosophila melanogaster Homo sapiens

Disease mentions