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

Abstract

The DNA binding protein KRC (for κB 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 κB motif and contains two widely separated DNA binding structures. In addition to the κB 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 P34cdc2 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 κB-controlled gene regulatory elements.