CK2 beta, which inhibits Mos function, binds to a discrete domain in the N-terminus of Mos.
Progesterone stimulates G2-arrested Xenopus oocytes to synthesize Mos, a MAPK kinase kinase required for the coordinated activation of cdc2 and the G2/Meiosis I (MI) transition. Mos leads to activation of MAPK, Rsk, and the inhibition of the cdc2 inhibitor Myt1. Previous work identified CK2 beta as a Mos-interacting protein, and suggested that CK2 beta acts as a negative regulator by setting a threshold above which newly made Mos must accumulate to activate MAPK. However, it had not been demonstrated that CK2 beta directly inhibits Mos. We report here that Mos (52-115) is required for CK2 beta binding and can serve as a portable binding domain. To test whether CK2 beta acts at the level of Mos or on a downstream component, we took advantage of previous work that showed injection of Mos arrests rapidly dividing embryonic cells. We find that coinjection of CK2 beta and Mos into embryonic cells inhibits the ability of Mos to arrest cell division. In contrast, CK2 beta does not inhibit the mitotic arrest induced by injection of active Rsk. These results argue that CK2 beta directly binds and inhibits Mos rather than a downstream component, and support that CK2 beta functions as a molecular buffer that prevents premature MAPK activation and oocyte maturation.
Lieberman
Soyan L
SL
Department of Cell Biology, Harvard Medical School, Boston MA 02115, USA.
Ruderman
Joan V
JV
D000818:Animals; D047390:Casein Kinase II; D002455:Cell Division / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000502:physiology; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017231:Proto-Oncogene Proteins c-mos / Q000037:antagonists & inhibitors*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D014981:Xenopus
D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D017231:Proto-Oncogene Proteins c-mos; D038744:Ribosomal Protein S6 Kinases, 90-kDa