Jun kinase phosphorylates and regulates the DNA binding activity of an octamer binding protein, T-cell factor beta 1

POU domain proteins have been implicated as key regulators during developme nt and lymphocyte activation. The POU domain protein T-cell factor beta 1 ( TCF beta 1), which binds octamer and octamer-related sequences, is a potent transactivator. In this study, we showed that TCF beta 1 is phosphorylated following activation via the T-cell receptor or by stress-induced signals. Phosphorylation of TCF beta 1 occurred predominantly at serine and threoni ne residues. Signals which upregulate Jun kinase (JNK)/stress-activated pro tein kinase activity also lead to association of JNK with TCF beta 1. JNK a ssociates with the activation domain of TCF beta 1 and phosphorylates its D NA binding domain. The phosphorylation of recombinant TCF beta 1 by recombi nant JNK enhances the ability of TCF beta 1 to bind to a consensus octamer motif. Consistent with this conclusion, TCF beta 1 upregulates reporter gen e transcription in an activation- and JNK-dependent manner. In addition, in hibition of JNK activity by catalytically inactive MEKK (in which methionin e was substituted for the lysine at position 432) also inhibits the ability of TCF beta 1 to drive inducible transcription from the interleukin-2 prom oter. These results suggest that stress-induced signals and T-cell activati on induce JNK, which then acts on multiple cis sequences by modulating dist inct transactivators like c-Jun and TCF beta 1. This demonstrates a couplin g between the JNK activation pathway and POU domain proteins and implicates TCF beta 1 as a physiological target in the JNK signal transduction pathwa y leading to coordinated biological responses.