Introduction One of the most miraculous events that occur in biology is the ability of a single cell, the fertilized egg, to be able to reproduce billions of cells and create a human being. In order for the egg to be transformed into organs and many specialized cells, it has to undergo many signaling pathways. One of the signaling pathways involved in this process in the Wnt signaling pathway. Due to the importance of this pathway, the Wnt signaling pathway is extremely conserved from an evolutionary standpoint. The Wnt proteins are used to regulate cellular communication during development and are also used in adults for adult tissue homeostasis. During development, the Wnt proteins are used to regulate stem cell pluripotency as well …show more content…
With the Wnt protein binding to the Fz/LRP receptor complex this initiates the stabilization of β-catenin. Stabilizing β-catenin allows for the β-catenin to enter into the nucleus of a cell and induce transcription for a Wnt target gene (5, 10).
First off, without the Wnt protein binding to the Fz/LRP receptor, the β-catenin is degraded by the adenomatous polyposis coli (APC)/ axin complex, also called the destruction complex. The APC/axin complex is made up of four proteins, APC, casein kinase 1 (CK1), axin, and glycogen synthase kinase 3 (GSK3). The axin plays a major role in regulating the Wnt signaling pathway. When Wnt is not bound to the Fz/LRP receptor, axin binds with the other proteins in the destruction complex and allows for CK1 and GSK3 to phosphorylate β-catenin which causes β-catenin to be ubiquinated and destroyed by proteasomes through interactions with β-TRCP. By having β-catenin destroyed, it can no longer function as a transcription factor for the Wnt target genes (1, …show more content…
The first step to the pathway is that once Fz/LRP complex is activated, LRP becomes phosphorylated and the PIP2 helps bring axin from the APC/axin complex to bind with LRP. This binding allows LRP to directing inhibit GSK3 and stops the phosphorylation of the β-catenin (3). With axin bound to LRP and the Fz receptor now activated, as well, due to Wnt binding, Fz can now recruit the Dishevelled protein (Dsh). Dsh is now activated by phosphorylation because of a number of kinases including CK1. The Dsh protein is made up of three regions which consist of DIX, PDZ, and DEP. When Dsh is activated it now inhibits GSK3 directly from the destruction complex, and activates a series of enzymes that help stabilize β-catenin and stops it from being degraded (5, 10). Now that β-catenin is stopped from phosphorylation and degradation, it can now accumulate in the cytosol where it undergoes changes from Ran-binding protein3 (RanBP3) and APC which allows β-catenin to now enter the nucleus