Complexes of p21RAS with JUN N-terminal kinase and JUN proteins.
RAS gene-encoded p21 protein has been found to increase in vitro phosphorylation of JUN via its kinase, JUN N-terminal kinase (JNK). This effect is mediated by increased phosphorylation of JNK in the presence of wild-type and oncogenic (Val-12) p21 protein in a dose-dependent manner. Oncogenic p21 protein is more potent in mediating this effect than its normal counterpart. Both normal and oncogenic p21 proteins bind to purified JNK and to JNK that is present in cell extracts from transformed fibroblasts and melanoma cells. Oncogenic and normal p21 proteins have also been found to bind to bacterially expressed JUN protein. This binding is dose dependent, enhanced by the presence of GTP, and depends on the presence of the first 89 amino acids of JUN (the delta domain), as it does not occur with v-jun. While the ability of both normal and oncogenic p21 proteins to bind JNK is strongly inhibited by a p21 peptide corresponding to aa 96-110, and more weakly inhibited by the p21 peptide corresponding to aa 115-126, p21-JUN interaction is inhibited by peptides corresponding to aa 96-110 and, to a lesser degree, by peptides corresponding to aa 35-47. The results suggest that the p21 protein interacts specifically with both JNK and JUN proteins.
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins