Stabilisation of β-catenin downstream of T cell receptor signalling

PLoS One. 2010 Sep 16;5(9):e12794. doi: 10.1371/journal.pone.0012794.


Background: The role of TCF/β-catenin signalling in T cell development is well established, but important roles in mature T cells have only recently come to light.

Methodology/principal findings: Here we have investigated the signalling pathways that are involved in the regulation of β-catenin in primary human T cells. We demonstrate that β-catenin expression is upregulated rapidly after T cell receptor (TCR) stimulation and that this involves protein stabilisation rather than an increase in mRNA levels. Similar to events in Wnt signalling, the increase in β-catenin coincides with an inhibition of GSK3, the kinase that is required for β-catenin degradation. β-catenin stabilisation in T cells can also be induced by the activation of PKC with phorbol esters and is blocked by inhibitors of phosphatidylinositol 3-kinase (PI3K) and phospholipase C (PKC). Upon TCR signalling, β-catenin accumulates in the nucleus and, parallel to this, the ratio of TCF1 isoforms is shifted in favour of the longer β-catenin binding isoforms. However, phosphorylated β-catenin, which is believed to be inactive, can also be detected and the expression of Wnt target genes Axin2 and dickkopf is down regulated.

Conclusions/significance: These data show that in mature human T cells, TCR signalling via PI3K and PKC can result in the stabilisation of β-catenin, allowing β-catenin to migrate to the nucleus. They further highlight important differences between β-catenin activities in TCR and Wnt signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Humans
  • Phosphorylation
  • Protein Stability
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction*
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / metabolism*
  • Up-Regulation
  • beta Catenin / genetics
  • beta Catenin / metabolism*


  • Receptors, Antigen, T-Cell
  • beta Catenin