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.