Evidence that fold-change, and not absolute level, of beta-catenin dictates Wnt signaling

Mol Cell. 2009 Dec 11;36(5):872-84. doi: 10.1016/j.molcel.2009.11.017.

Abstract

In response to Wnt stimulation, beta-catenin accumulates and activates target genes. Using modeling and experimental analysis, we found that the level of beta-catenin is sensitive to perturbations in the pathway, such that cellular variation would be expected to alter the signaling outcome. One unusual parameter was robust: the fold-change in beta-catenin level (post-Wnt/pre-Wnt). In Xenopus, dorsal-anterior development and target gene expression are robust to perturbations that alter the final level but leave the fold-change intact. These suggest, first, that despite cellular noise, the cell responds reliably to Wnt stimulation by maintaining a robust fold-change in beta-catenin. Second, the transcriptional machinery downstream of the Wnt pathway does not simply read the beta-catenin level after Wnt stimulation but computes fold-changes in beta-catenin. Analogous to Weber's Law in sensory physiology, some gene transcription networks must respond to fold-changes in signals, rather than absolute levels, which may buffer stochastic, genetic, and environmental variation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Embryo, Nonmammalian / metabolism
  • Humans
  • Models, Theoretical
  • Signal Transduction*
  • Wnt Proteins / metabolism*
  • Xenopus
  • beta Catenin / metabolism*

Substances

  • Wnt Proteins
  • beta Catenin
pFad - Phonifier reborn

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.

Note: This service is not intended for secure transactions such as banking, social media, email, or purchasing. Use at your own risk. We assume no liability whatsoever for broken pages.


Alternative Proxies:

Alternative Proxy

pFad Proxy

pFad v3 Proxy

pFad v4 Proxy