Re-evaluating the role of Frat in Wnt-signal transduction

Cell Cycle. 2005 Aug;4(8):1065-72. Epub 2005 Aug 1.

Abstract

Frat proteins are potent activators of canonical Wnt-signal transduction. By binding to GSK3, Frat prevents the phosphorylation and concomitant degradation of beta-catenin and allows the activation of downstream target genes by beta-catenin/TCF complexes. The identification of the Xenopus Frat homologue GBP as an essential component of the maternal Wnt-pathway during embryonic axis formation suggested that Frat might fulfill a similar role in higher vertebrates. As a result most, if not all, studies addressing Frat function have focused on its ability to bind GSK3 and induce signaling through beta-catenin/TCF. Consequently, Frat has been advocated as the "missing link" that bridged signaling from Dishevelled to GSK3 in the canonical Wnt-pathway. Recent mouse-knockout studies however, call for a reevaluation of the physiological role of Frat. Mice that lack all Frat-family members appear to be normal and display no obvious defects in beta-catenin/TCF signaling. This observation reopens the question as to how GSK3 activity is controlled in vertebrate canonical Wnt-signal transduction in view of the apparent dispensability of Frat. Here we will review the studies that have been conducted on Frat proteins to date, with a specific focus on those that implicate a role for Frat in Wnt-signal transduction. In addition, we will discuss potential alternatives for the endogenous function of Frat.

Publication types

  • Review

MeSH terms

  • Alleles
  • Amino Acid Motifs
  • Animals
  • Caenorhabditis elegans
  • Cell Line, Tumor
  • Drosophila
  • Gene Expression Regulation*
  • Genes, Reporter
  • Glycogen Synthase Kinase 3 / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Luciferases / metabolism
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Phosphorylation
  • Protein Conformation
  • Proto-Oncogene Proteins / physiology*
  • Signal Transduction*
  • Wnt Proteins / metabolism*
  • Xenopus
  • beta Catenin / metabolism

Substances

  • FRAT1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins
  • Wnt Proteins
  • beta Catenin
  • Luciferases
  • Glycogen Synthase Kinase 3