Differences in patterns of activation of MAP kinases induced by oncogenic ras-p21 and insulin in oocytes

Oncogenic ras (Val 12-containing)-p21 protein induces oocyte maturation by a pathway that is blocked by peptides from effector domains of ras-p21, i.e ., residues 35-47 (that block Val 12-p21-activated raf) and 96-110 and 115- 126, which do not affect the ability of insulin-activated cellular p21 to i nduce maturation. Oncogenic p21 binds directly to jun-N-terminal kinase (JN K), which is blocked by the p21 96-110 and 115-126 peptides. This finding p redicts that oncogenic p21, but not insulin, induces maturation by early an d sustained activation of JNK. We now directly confirm this prediction by s howing that oncogenic p21 induces activating phosphorylation of JNK (JNK-P) and of ERK (MAP kinase) (MAPK-P), whose levels correlate with oocyte matur ation. p21 peptides 35-47 and 96-110 block formation of JNK-P and MAK-P, fu rther confirming this correlation and suggesting, unexpectedly, that raf-ME K-MAPK and JNK-jun pathways strongly interact on the oncogenic p21 pathway. In contrast, insulin activates only low levels of JNK-P, and, surprisingly , we find that insulin induces only low levels of MAPK-P, indicating that i nsulin and activated normal p21 utilize MAP kinase-independent signal trans duction pathways. (C) 2001 Academic Press.