EVIDENCE THAT SIGNAL-TRANSDUCTION BY ONCOGENIC RAS-P21 PROTEIN DEPENDS ON ITS INTERACTION WITH JUN KINASE AND JUN PROTEINS

ras oncogene-encoded p21 protein has been found to bind to jun-W-kinas e (JNK) and its substrate jun protein. Binding of p21 to jun occurs in the amino terminal domain of jun, residues 5-89. We now show that jun peptide 5-89 completely blocks oncogenic p21 protein-induced oocyte m aturation but only partially inhibits the induction of oocyte maturati on by insulin which activates normal, cellular ras, Thus, oncogenic an d normal p21 proteins utilise different signal transduction pathways. The ras-p21 peptide, corresponding to residues 96-110, has been found to block oncogenic p21 protein-induced oocyte maturation and to inhibi t the interaction of p21 with both JNK and jun proteins. Dose response curves for oocyte inhibition and inhibition of ras-JNK and uas-jun in teraction coincide with one another, suggesting that this peptide bloc ks ras induction of oocyte maturation by blocking its interaction with JNK and jun. Thus JNK and jun are critical targets of oncogenic p21 p rotein in mitogenic signal transduction.