Regulation by phosphorylation of the zinc finger protein KRC that binds the kappaB motif and V(D)J recombination signal sequences.
The DNA binding protein KRC (forkappaB binding andrecognitioncomponent of the V(D)J recombination signal sequence) belongs to a family of large zinc finger proteins that bind to the kappaB motif and contains two widely separated DNA binding structures. In addition to the kappaB 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 kappaB-controlled gene regulatory elements.
Bachmeyer
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Department of Internal Medicine and Department of Medical Biochemistry, Ohio State University, Columbus, OH 43210, USA.
Mak
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CH
Yu
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Wu
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D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000032:analysis; D019000:Phosphotyrosine / Q000032:analysis; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D045567:VDJ Recombinases; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C084779:Hivep3 protein, mouse; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D010768:Phosphoserine; D019000:Phosphotyrosine; D011494:Protein Kinases; D066246:ErbB Receptors; D016203:CDC2 Protein Kinase; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases