CKII (formerly known as casein kinase LI) is a ubiquitously expressed enzyme that plays an important role in regulating cell growth and differentiation. The beta subunit of CKII (CKII beta) is not catalytic but forms heterotetramers with the catalytic subunit a to generate an alpha(2) beta(2) holoenzyme. In Xenopus oocytes, CKII beta also associates with another serine/threonine kinase, Mos, As a key regulator of meiosis, Mos is necessary and sufficient to initiate oocyte maturation, We have previously shown that the binding of CKII beta to Mos represses Mos-mediated mitogen-activated protein kinase (MAPK) activation and that the ectopic expression of CKII beta inhibits progesterone-induced Xenopus oocyte maturation, We have now used an antisense oligonucleotide technique to reduce the endogenous CKII beta protein level in Xenopus oocytes, and we find that oocytes with a reduced content of CKII beta are more sensitive to low doses of progesterone and show accelerated MAPK activation and germinal vesicle breakdown, Furthermore, ectopic expression of a Mos-binding fragment of CKII beta suppressed the effect of antisense oligonucleotide, These results suggest that the endogenous CKII beta normally sets a threshold level for Mos protein, which must be exceeded for Mos to activate the MAPK signaling pathway and induce oocyte maturation.