Mutual dependence of jun-N-terminal kinase and protein kinase C on the oncogenic ras-p21 protein-induced mitogenic signalling pathway

We have previously presented evidence that there is a distinct oncogenic ras-p21 protein mitogenic signal transduction pathway causing maturation of oocytes. This pathway involves a direct interaction between p21 and jun-N terminal kinase (JNK) and its target, jun protein and activation of protein kinase C (PKC). The question arises as to the relationship between JNK and PKC on the oncogenic ras-p21 signal transduction pathway. We have now found that a selective inhibitor of PKC, CGP 41 251, blocks JNK-induced oocyte maturation and that a newly isolated JNK inhibitory protein of Mr 26 kDa blocks PKC-induced oocyte maturation. This reciprocal inhibition of JNK by a PKC inhibitor and PKC by a JNK inhibitor suggests that each protein requires the activation of the other protein. A possible explanation of the mutual activation requirement is that both proteins activate jun. Phosphorylation of jun by one protein may facilitate phosphorylation by the other protein. That jun is critical on the oncogenic ras pathway is supported by the finding that a dominant negative mutant of jun blocks ras-p21-induced oocyte maturation in a specific manner.