Kosako H, Gotoh Y, Nishida E
Department of Genetics and Molecular Biology, Kyoto University, Japan.
J Biol Chem. 1994 Nov 11;269(45):28354-8.
The product of the c-mos proto-oncogene functions not only as an initiator of oocyte maturation but also as a component of cytostatic factor that causes the natural arrest of the unfertilized egg at the second meiotic metaphase. It has been shown that Mos can phosphorylate and activate mitogen-activated protein (MAP) kinase kinase (MAPKK) in vitro, leading to activation of MAP kinase. In this study, by using an anti-MAPKK antibody that can specifically inhibit Xenopus MAPKK activity, we have shown that MAPKK mediates the cytostatic factor activity of Mos. Coinjection of this anti-MAPKK antibody with the bacterially expressed Mos protein into a two-cell embryo prevented the Mos-induced cleavage arrest as well as the Mos-induced MAP kinase activation. The analysis of individual embryos indicated that the degree of the cleavage arrest was correlated with the extent of the MAP kinase activation in the Mos- and the Mos/antibody-injected embryos. These observations suggest the involvement of a signal transmission pathway consisting of Mos, MAPKK, and MAP kinase in the metaphase arrest.
原癌基因c-mos的产物不仅作为卵母细胞成熟的启动因子发挥作用，还作为细胞静止因子的一个组成部分，使未受精卵在第二次减数分裂中期自然停滞。研究表明，Mos在体外可磷酸化并激活丝裂原活化蛋白（MAP）激酶激酶（MAPKK），从而导致MAP激酶的激活。在本研究中，通过使用一种能够特异性抑制非洲爪蟾MAPKK活性的抗MAPKK抗体，我们证明了MAPKK介导了Mos的细胞静止因子活性。将这种抗MAPKK抗体与细菌表达的Mos蛋白共同注射到二细胞胚胎中，可防止Mos诱导的卵裂停滞以及Mos诱导的MAP激酶激活。对单个胚胎的分析表明，在注射Mos和Mos/抗体的胚胎中，卵裂停滞的程度与MAP激酶激活的程度相关。这些观察结果提示，由Mos、MAPKK和MAP激酶组成的信号转导通路参与了中期停滞过程。
