HA-RASVAL-12,THR-59 ACTIVATES S6 KINASE AND P34CDC2 KINASE IN XENOPUS OOCYTES - EVIDENCE FOR C-MOSXE-DEPENDENT AND C-MOSXE-INDEPENDENT PATHWAYS

Treatment with insulin or progesterone or microinjection of the transforming protein product of Ha-ras(Val-12,Thr-59) (p21) is known to induce germinal vesicle breakdown in Xenopus oocytes. We have investigated the effect of p21 on S6 kinase and the H1 histone kinase of maturation-promoting factor in the presence and absence of antisense oligonucleotides against the c-mos(xe) proto-oncogene. Injection of p21 led to a rapid increase in S6 phosphorylation, with kinetics similar to those previously observed with insulin. Microinjection of c-mos(xe) antisense oligonucleotides inhibited germinal vesicle breakdown induced by p21 and totally abolished S6 kinase activation by insulin or progesterone but only partially inhibited activation by p21. However, the activation of p34(cdc2) protein kinase by all three stimuli was blocked by antisense oligonucleotides. The results suggest that in oocyte maturation c-mos(xe) functions downstream of p21 but upstream of p34(cdc2) and S6 kinase activation, although not all p21-induced events require c-mos(xe).