MUTUAL DEPENDENCE OF JUN-N-TERMINAL KINASE AND PROTEIN-KINASE-C ON THE ONCOGENIC RAS-P21 PROTEIN-INDUCED MITOGENIC SIGNALING PATHWAY

We have previously presented evidence that there is a distinct oncogen ic ras-p21 protein mitogenic signal transduction pathway causing matur ation of oocytes. This pathway involves a direct interaction between p 21 and jun-N terminal kinase (JNK) and its target, jun protein and act ivation of protein kinase C (PKC). The question arises as to the relat ionship between JNK and PKC on the oncogenic ras-p21 signal transducti on pathway. We have now found that a selective inhibitor of PKC, CGP 4 1 251, blocks JNK-induced oocyte maturation and that a newly isolated JNK inhibitory protein of Mr 26 kDa blocks PKC-induced oocyte maturati on. This reciprocal inhibition of JNK by a PKC inhibitor and PKC by a JNK inhibitor suggests that each protein requires the activation of th e other protein. A possible explanation of the mutual activation requi rement is that both proteins activate jun. Phosphorylation of jun by o ne protein may facilitate phosphorylation by the other protein. That j un is critical on the oncogenic ras pathway is supported by the findin g that a dominant negative mutant of jun blocks ras-p21 -induced oocyt e maturation in a specific manner. (C) 1998 Chapman & Hall Ltd.