A peptide encoding the c-Jun delta domain inhibits the activity of a c-jun amino-terminal protein kinase.
Evidence suggests that the c-Jun protooncogene delta (delta) domain (amino acids 31-60) helps regulate the transcriptional activating capacity of c-Jun by modulating the amino-terminal phosphorylation of this protein. By using a peptide encoding the delta domain and purified amino-terminal c-Jun protein kinase, we demonstrate that the delta domain peptide inhibits phosphorylation of the amino terminus of both c-Jun and the related protein JunD. The delta domain peptide inhibited the activation of the c-Jun amino-terminal protein kinase by phorbol esters in permeabilized U937 leukemic cells. Mutation of c-Jun followed by transfection into U937 leukemic cells demonstrated that partial deletions of the delta domain are sufficient to block phosphorylation of the amino terminus of c-Jun. In vitro deletion of the amino-terminal (amino acids 31-44) half of the delta domain inhibited the phosphorylation of c-Jun. However, deletion of the carboxyl-terminal (amino acids 45-60) half only partially inhibited c-Jun phosphorylation. Therefore, these results indicate that the delta domain sequence is an important regulator of c-Jun amino-terminal phosphorylation.
Adler
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Division of Hematology/Oncology, University of Alabama, Birmingham 35294.
Unlap
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Kraft
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D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D007938:Leukemia; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism* / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D010455:Peptides; D047428:Protein Kinase Inhibitors; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases