The casein kinase II beta subunit binds to Mos and inhibits Mos activity.
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 beta subunit of casein kinase II (CKII beta) binds to and regulates Mos. The Mos-interacting region of CKII beta was mapped to the C terminus. Mos bound to CKII beta in somatic cells ectopically expressing Mos and CKII beta as well as in unfertilized Xenopus eggs. CKII beta 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 CKII beta mRNA into Xenopus oocytes inhibited progesterone-induced meiotic maturation and MAPK activation, presumably by binding of CKII beta to Mos and thereby inhibiting MAPK activation. Moreover, this inhibitory phenotype could be rescued by another protein that binds to CKII beta, CKII alpha. The ability of ectopic CKII beta to inhibit meiotic maturation and the detection of a complex between endogenous Mos and CKII beta suggest that CKII beta 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.
Chen
M
M
Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.
Li
D
D
Krebs
E G
EG
Cooper
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D047390:Casein Kinase II; D017931:DNA Primers / Q000235:genetics; D004789:Enzyme Activation; D005260:Female; D066298:In Vitro Techniques; D020929:Mitogen-Activated Protein Kinase Kinases; D009865:Oocytes / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D010641:Phenotype; D011374:Progesterone / Q000494:pharmacology; D011487:Protein Conformation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017231:Proto-Oncogene Proteins c-mos / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
D017931:DNA Primers; D011374:Progesterone; D011494:Protein Kinases; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D017231:Proto-Oncogene Proteins c-mos; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases