Tcf-1-mediated transcription in T lymphocytes: differential role for glycogen synthase kinase-3 in fibroblasts and T cells

beta-Catenin is the vertebrate homolog of the Drosophila segment polarity g ene Armadillo and plays roles in both cell-cell adhesion and transduction o f the Wnt signaling cascade. Recently, members of the Lef/Tcf transcription factor family have been identified as protein partners of beta-catenin, ex plaining how beta-catenin alters gene expression. Here we report that in T cells, Tcf-1 also becomes transcriptionally active through interaction with beta-catenin, suggesting that the Wnt signal transduction pathway is opera tional in T lymphocytes as well. However, although Wnt signals are known to inhibit the activity of the negative regulatory protein kinase glycogen sy nthase kinase-3 beta (GSK-3 beta), resulting in increased levels of beta-ca tenin, we rind no evidence for involvement of GSK-3 beta in Tcf-mediated tr anscription in T cells. That is, a dominant negative GSK-3 beta does not sp ecifically activate Tcf transcription and stimuli (lithium or phytohemagglu tinin) that inhibit GSK-3 beta activity also do not activate Tcf reporter g enes. Thus, inhibition of GSK-3 beta is insufficient to activate Tcf-depend ent transcription in T lymphocytes, In contrast, in C57MG fibroblast cells, lithium inactivates GSK-3 beta and induces Tcf-controlled transcription. T his is the first demonstration that lithium can alter gene expression of Tc f-responsive genes, and points to a difference in regulation of Wnt signali ng between fibroblasts and lymphocytes.