Conklin D S, Galaktionov K, Beach D
Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, NY 11724, USA.
Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7892-6. doi: 10.1073/pnas.92.17.7892.
The cdc25 phosphatases play key roles in cell cycle progression by activating cyclin-dependent kinases. Two members of the 14-3-3 protein family have been isolated in a yeast two-hybrid screen designed to identify proteins that interact with the human cdc25A and cdc25B phosphatases. Genes encoding the human homolog of the 14-3-3 epsilon protein and the previously described 14-3-3 beta protein have been isolated in this screening. 14-3-3 proteins constitute a family of well-conserved eukaryotic proteins that were originally isolated in mammalian brain preparations and that possess diverse biochemical activities related to signal transduction. We present evidence that indicates that cdc25 and 14-3-3 proteins physically interact both in vitro and in vivo. 14-3-3 protein does not, however, affect the phosphatase activity of cdc25A. Raf-1, which is known to bind 14-3-3 proteins, has recently been shown to associate with cdc25A and to stimulate its phosphatase activity. 14-3-3 protein, however, has no effect on the cdc25A-kinase activity of Raf-1. Instead, 14-3-3 may facilitate the association of cdc25 with Raf-1 in vivo, participating in the linkage between mitogenic signaling and the cell cycle machinery.
细胞分裂周期蛋白25（cdc25）磷酸酶通过激活细胞周期蛋白依赖性激酶在细胞周期进程中发挥关键作用。在一项旨在鉴定与人类cdc25A和cdc25B磷酸酶相互作用的蛋白质的酵母双杂交筛选中，分离出了14-3-3蛋白家族的两个成员。在该筛选中，已分离出编码14-3-3ε蛋白的人类同源物和先前描述的14-3-3β蛋白的基因。14-3-3蛋白构成了一个高度保守的真核蛋白家族，最初是在哺乳动物脑组织提取物中分离出来的，并且具有与信号转导相关的多种生化活性。我们提供的证据表明，cdc25蛋白和14-3-3蛋白在体外和体内均存在物理相互作用。然而，14-3-3蛋白并不影响cdc25A的磷酸酶活性。已知与14-3-3蛋白结合的Raf-1最近被证明与cdc25A相关联并刺激其磷酸酶活性。然而，14-3-3蛋白对Raf-1的cdc25A激酶活性没有影响。相反，14-3-3可能在体内促进cdc25与Raf-1的结合，参与有丝分裂信号传导与细胞周期机制之间的联系。
