Figure: Wnt1 signalling

Introduction

For degradation of beta-catenin, it is first phosphorylated by casein kinase 1-alpha or protein kinase A on Ser-45. This is followed by phosphorylation on amino acid residues 33/37/41 by glycogen synthase kinase 3 which results in recognition by beta-TrCP and targeting for proteosomal degradation, preventing effects on nuclear transcription factors or binding to surface cadherins.

Wnt1 activation of frizzled leads to DSH/GBP (dishevelled/GSK3 binding protein) complex inhibiting GSK3 when GSK3 is associated with axin and casein kinase 1 alpha. The GSK3-presenilin-PKA complex is not affected by wnt1.

Pin-1 inhibits interaction of APC with beta-catenin.

Downstream genes include c-myc, c-jun, cyclin D1, PPAR-gamma, MMP-7, axin-2 and CD44.