Question

answer both questions

Cell Signaling Pathways - A Case Study Approach L. Emtage, L. Bradbury, N. Coleman, D. Davenport, A. Dunning and I Grew Assignment: The Wnt/ b-catenin pathway zd Plasma membrane Ubiquitin-mediated degradation pratenin B-catenin B-catenin TCF MIDI 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.

Answer 1

ANS 7 - Frizzled is the transmembrane receptor in Wnt signaling pathway when Wnt Binds to frizzled receptor than it activates or phosphorylate intermediate Dishevelleds with the help of co receptor LRP5/6 (low-density lipoprotein receptor-related proteins). Dishevelleds further phosphorylate β-catenin destruction complex which will inhibit the phosphorylation of β-catenin in cytoplasm and β-catenin translocate inside nucleus and activates WNT target proteins for cell proliferation and cell differentiation.

In absence of Wnt Ligand Phosphorylation of β-catenin takes place by β-catenin destruction complex which will recognized and Ubiquitinated with the help of ubiquitin ligase enzyme then goes to proteolysis for degradation.

β-catenin destruction complex consist of Auxin ,adenomatous polyposis coli, glycogen synthase kinase-3 beta and casein kinase-1. If their is any kind of Loss of function mutation in this protein will lead to deactivation of β-catenin destruction complex which will not further phosphorylate β-catenin for degradation leads to increase in β-catenin in cytoplasm which will translocate inside nucleus and activates Wnt signal Target proteins require for cell proliferation and Differentiation. Cell may go in oncogenic state if Loss of function mutation observe in β-catenin destruction complex.

Ans 8 - After the Translation of wnt protein goes to post translation modification - Acetylation in endoplasmic reticulam by Porcupine and Wnt protein is secreted in vessicle by multi-pass transmembrane protein. After the release of wnt from cell interaction of wnt with wnt receptor(Frizzled) is important.