Abstract
Background: The role of TCF/beta-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 beta-catenin in primary human T cells. We demonstrate that beta-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 beta-catenin coincides with an inhibition of GSK3, the kinase that is required for beta-catenin degradation. beta-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, b-catenin accumulates in the nucleus and, parallel to this, the ratio of TCF1 isoforms is shifted in favour of the longer beta-catenin binding isoforms. However, phosphorylated beta-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 beta-catenin, allowing beta-catenin to migrate to the nucleus. They further highlight important differences between beta-catenin activities in TCR and Wnt signalling.
| Original language | English |
|---|---|
| Article number | e12794 |
| Journal | PL o S One |
| Volume | 5 |
| Issue number | 9 |
| Publication status | Published - 2010 |