Wu L, Russell P
Department of Molecular Biology, Scripps Research Institute, La Jolla 92037.
Nature. 1993 Jun 24;363(6431):738-41. doi: 10.1038/363738a0.
In most species, including the fission yeast Schizosaccharomyces pombe, the Cdc2/cyclin B mitosis-inducing kinase is maintained in an inhibited state during interphase as a result of phosphorylation of a tyrosine residue in the ATP-binding region of Cdc2 (refs 1-3). This site is phosphorylated by Wee1 kinase and dephosphorylated by Cdc25 phosphatase. In fission yeast an additional element of the G2/M control Nim1/Cdr1 kinase, has been identified which functions as a potent mitotic inducer. These studies suggested that Nim1 acts by inhibiting Wee1, perhaps by direct phosphorylation. Consistent with this model, we report here that Wee1 is hyperphosphorylated in cells that overproduce Nim1. Likewise, Wee1 phosphorylation is reduced in nim1- cells. Highly purified Nim1 kinase phosphorylates Wee1 in vitro, resulting in strong inhibition of Wee1 kinase. These observations show that Nim1 promotes the onset of mitosis by inhibiting Wee1.
在大多数物种中，包括裂殖酵母粟酒裂殖酵母，Cdc2/细胞周期蛋白B促有丝分裂激酶在间期由于Cdc2的ATP结合区域中的酪氨酸残基磷酸化而维持在抑制状态（参考文献1-3）。该位点由Wee1激酶磷酸化，并由Cdc25磷酸酶去磷酸化。在裂殖酵母中，已鉴定出G2/M控制的另一个元件Nim1/Cdr1激酶，其作为一种有效的有丝分裂诱导剂发挥作用。这些研究表明，Nim1可能通过直接磷酸化来抑制Wee1发挥作用。与此模型一致，我们在此报告，在过量产生Nim1的细胞中，Wee1发生了过度磷酸化。同样，在nim1-细胞中，Wee1磷酸化减少。高度纯化的Nim1激酶在体外使Wee1磷酸化，导致Wee1激酶受到强烈抑制。这些观察结果表明，Nim1通过抑制Wee1来促进有丝分裂的开始。
