Regulation by phosphorylation of the zinc finger protein KRC that binds the kappa B motif and V(D)J recombination signal sequences

The DNA binding protein KRC (for <(kappa)under bar>B binding and recognitio n component of the V(D)J recombination signal sequence) belongs to a family of large zinc finger proteins that bind to the kappa B motif and contains two widely separated DNA binding structures. In addition to the kappa B mot if, KRC fusion proteins bind to the signal sequences of V(D)J recombination to form highly ordered complexes. Here, we report that KRC may be regulate d by post-translational modifications. Specific protein kinases present in the nucleus of pre-B cells phosphorylated a KRC fusion protein at tyrosine and serine residues. Such protein modifications increased DNA binding, ther eby providing a mechanism by which KRC responds to signal transduction path ways. KRC is a substrate of epidermal growth factor receptor kinase and P(3 4)cdc2 kinase in vitro. Our results suggest that activation of the KRC fami ly of transcription factors may provide a mechanism by which oncogenic tyro sine kinases regulate genes with kappa B-controlled gene regulatory element s.