The Casein Kinase II β Subunit Binds to Mos and Inhibits Mos Activity

Abstract

Mos is a germ cell-specific serine/threonine kinase and is required for Xenopus oocyte maturation. Active Mos stimulates a mitogen-activated protein kinase (MAPK) by directly phosphorylating and activating MAPK kinase (MKK). We report here that the Xenopus homolog of the β subunit of casein kinase II (CKIIβ) binds to and regulates Mos. The Mos-interacting region of CKIIβ was mapped to the C terminus. Mos bound to CKIIβ in somatic cells ectopically expressing Mos and CKIIβ as well as in unfertilized Xenopus eggs. CKIIβ inhibited Mos-mediated MAPK activation in rabbit reticulocyte lysates and repressed MKK activation by v-Mos in a coupled kinase assay. In addition, microinjection of CKIIβ mRNA into Xenopus oocytes inhibited progesterone-induced meiotic maturation and MAPK activation, presumably by binding of CKIIβ to Mos and thereby inhibiting MAPK activation. Moreover, this inhibitory phenotype could be rescued by another protein that binds to CKIIβ, CKIIα. The ability of ectopic CKIIβ to inhibit meiotic maturation and the detection of a complex between endogenous Mos and CKIIβ suggest that CKIIβ may act as an inhibitor of Mos during oocyte maturation, perhaps setting a threshold beyond which Mos protein must accumulate before it can activate the MAPK pathway.