Kusubata M, Tokui T, Matsuoka Y, Okumura E, Tachibana K, Hisanaga S, Kishimoto T, Yasuda H, Kamijo M, Ohba Y
Department of Neurophysiology, Tokyo Metropolitan Institute of Gerontology, Japan.
J Biol Chem. 1992 Oct 15;267(29):20937-42.
The regulation of p34cdc2 kinase activity controls the entry into and exit from mitosis. Although genetic and biochemical evidence suggested close interactions between cyclins, p13suc1 and p34cdc2 kinase, the roles of p13suc1 on p34cdc2 kinase functions remain unclear. To examine the effects of p13suc1 on p34cdc2 kinase function we developed a simple purification procedure for p34cdc2 kinase, unassociated with p13suc1. The key to the purification procedures we used was buffer containing 0.5 M NaCl and 50% ethylene glycol, as a specific elutant of p34cdc2 kinase from p13suc1-Sepharose. This purified p34cdc2 kinase stoichiometrically phosphorylated vimentin and desmin. Exogenous p13suc1 suppressed the phosphorylation of these filament proteins by the kinase and prevented disassembly, although histone H1 phosphorylation was not affected. Peptide mapping analysis showed a similar extent of inhibition by p13suc1 for all five phosphorylation sites by p34cdc2 kinase of vimentin and desmin, hence these p13suc1-induced inhibitions are probably not site-specific. It thus appears that p13suc1 has a selective effect on the catalytic activity of p34cdc2 kinase for these filament proteins.
p34cdc2激酶活性的调控控制着有丝分裂的进出。尽管遗传学和生物化学证据表明细胞周期蛋白、p13suc1和p34cdc2激酶之间存在密切相互作用,但p13suc1在p34cdc2激酶功能中的作用仍不清楚。为了研究p13suc1对p34cdc2激酶功能的影响,我们开发了一种简单的p34cdc2激酶纯化方法,该方法与p13suc1不相关。我们使用的纯化方法的关键是含有0.5 M NaCl和50%乙二醇的缓冲液,作为从p13suc1-琼脂糖中特异性洗脱p34cdc2激酶的洗脱剂。这种纯化的p34cdc2激酶能化学计量地磷酸化波形蛋白和结蛋白。外源性p13suc1抑制了该激酶对这些丝状蛋白的磷酸化并阻止了解聚,尽管组蛋白H1磷酸化不受影响。肽图分析表明,p13suc1对波形蛋白和结蛋白的p34cdc2激酶的所有五个磷酸化位点的抑制程度相似,因此这些p13suc1诱导的抑制可能不是位点特异性的。因此,p13suc1似乎对p34cdc2激酶对这些丝状蛋白的催化活性具有选择性作用。