Stabilisation of β-catenin downstream of T cell receptor signalling.
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.


RESULTS
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
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.
Lovatt
Matthew
M
Peter Gorer Department of Immunobiology, School of Medicine at Guy's, King's College and St Thomas' Hospitals, King's College London, Guy's Hospital, London, UK. matthew.lovatt@imb.a-star.edu.sg
Bijlmakers
Marie-José
MJ
D002478:Cells, Cultured; D006801:Humans; D010766:Phosphorylation; D055550:Protein Stability; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000737:chemistry / Q000378:metabolism*; D015854:Up-Regulation; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D011948:Receptors, Antigen, T-Cell; D051176:beta Catenin