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

The DNA binding protein KRC (for <(kappa)under bar>B binding and recognition 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 motif, 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 regulated 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, thereby providing a mechanism by which KRC responds to signal transduction pathways. KRC is a substrate of epidermal growth factor receptor kinase and P(34)cdc2 kinase in vitro. Our results suggest that activation of the KRC family of transcription factors may provide a mechanism by which oncogenic tyrosine kinases regulate genes with kappa B-controlled gene regulatory elements.