COMPLEXES OF P21(RAS) WITH JUN N-TERMINAL KINASE AND JUN PROTEINS

RAS gene-encoded p21 protein has been found to increase in vitro phosp horylation of JUN via its kinase, JUN N-terminal kinase (JNK), This ef fect is mediated by increased phosphorylation of JNK in the presence o f wild-type and oncogenic (Val-12) p21 protein in a dose-dependent man ner, Oncogenic p21 protein is more potent in mediating this effect tha n its normal counterpart, Both normal and oncogenic p21 proteins bind to purified JNK and to JNK that is present in cell extracts from trans formed fibroblasts and melanoma cells, Oncogenic and normal p21 protei ns have also been found to bind to bacterially expressed JUN protein, This binding is dose dependent, enhanced by the presence of GTP, and d epends on the presence of the first 89 amino acids of JUN (the delta d omain), as it does not occur with v-jun, While the ability of both nor mal and oncogenic p21 proteins to bind JNK is strongly inhibited by a p21 peptide corresponding to aa 96-110, and more weakly inhibited by t he p21 peptide corresponding to aa 115-126, p21-JUN interaction is inh ibited by peptides corresponding to aa 96-110 and, to a lesser degree, by peptides corresponding to aa 35-47, The results suggest that the p 21 protein interacts specifically with both JNK and JUN proteins.