Lieberman Soyan L, Ruderman Joan V
Department of Cell Biology, Harvard Medical School, Boston MA 02115, USA.
Dev Biol. 2004 Apr 15;268(2):271-9. doi: 10.1016/j.ydbio.2003.12.009.
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.
孕酮刺激处于G2期停滞的非洲爪蟾卵母细胞合成Mos，Mos是一种丝裂原活化蛋白激酶激酶激酶，对于协调激活细胞周期蛋白依赖性激酶2（cdc2）和G2期/减数分裂I（MI）转换是必需的。Mos导致丝裂原活化蛋白激酶（MAPK）、核糖体S6激酶（Rsk）的激活以及cdc2抑制剂Myt1的抑制。先前的研究确定酪蛋白激酶2β（CK2β）是一种与Mos相互作用的蛋白，并表明CK2β作为负调节因子，通过设定一个阈值来发挥作用，超过该阈值新合成的Mos必须积累才能激活MAPK。然而，尚未证明CK2β直接抑制Mos。我们在此报告，Mos（52 - 115）是CK2β结合所必需的，并且可以作为一个可移植的结合结构域。为了测试CK2β是作用于Mos水平还是下游成分，我们利用了先前的研究结果，即注射Mos会使快速分裂的胚胎细胞停滞。我们发现将CK2β和Mos共同注射到胚胎细胞中会抑制Mos阻止细胞分裂的能力。相比之下，CK2β并不抑制注射活性Rsk诱导的有丝分裂停滞。这些结果表明CK2β直接结合并抑制Mos而非下游成分，并支持CK2β作为分子缓冲剂发挥作用，防止MAPK过早激活和卵母细胞成熟。
