Question

Cell Signaling Pathways A Case Study Approach L. Emtage, L Bradbury, N. Coleman, D. Davenport. A Dunning and Grew Assignment. The Wnt/f-catenin pathway B-catenin B-catenin TO Note: GSK3, APC and Axin together are called the B-catenin Destruction Complex DSH is the abbreviation for Dishevelled. The human genome encodes many Fzd receptors, several Dsh proteins, one GSK3, and one ß-catenin. Questions 1. What are the components of the receptor complex? What is the ligand? 2. What is the molecular function of B-catenin itself? 3. Where is B-catenin found within the cell? Does its subcellular location ever change? 4. What are the molecular functions of GSK3, APC, and Axin? 5. Describe the ultimate outcome of Wnt pathway activation 6. Give two examples of negative regulation found here. Contrast their molecular mechanisms 7. Describe the effect of loss-of-function mutations in Frizzled, DSH, GSK3, and B- catenin separately on the transcription of target genes. You can assume that mutations in any part of the B-catenin Destruction Complex will cause the loss of function of the entire complex. 8. What role would Notum play in this pathway? 9. What modifications are made to the Wnt ligand prior to secretion from the cell and what interaction, once secreted, is it important for?

Answer 1

Question 1

Answer: Wnt/β-catenin is a signalling pathway that leads to accumulation of β-catenin in the cell cytoplasm.  β-catenin later gets translocated to nucleus and activates transcriptional factors of LEF/TCH family. Wnt is the ligand that binds to receptor frizzled family receptor (fz). fz is a transmembrane protein that spans seven times. The main components of receptor includes fz (receptor) and lipoprotein receptor related protein (LPR)-5/6 (co-receptor).

Question 2

Answer: β-catenin is a protein that is involved in cell to cell adhension and acts as transcriptional co-activator that activates various transcriptional factors involved of LEF/TCH family.

Question 3

Answer: β-catenin is synthesized in the cytoplasm and hence it is found in the cytoplasm of the cell. Upon activation of Wnt/β-catenin signalling pathway, β-catenin is translocated to nucleus and activates transcriptional factors of LEF/TCH family. Hence its sub-cellular location is changed from cytoplasm to nucleus in the cell.