Cicirelli M F, Pelech S L, Krebs E G
Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle 98195.
J Biol Chem. 1988 Feb 5;263(4):2009-19.
A number of different protein and peptide substrates were used to identify and characterize stimulated kinase activities in Xenopus oocyte extracts prepared during the major burst in protein phosphorylation that precedes meiotic cell division. While total cAMP-dependent protein kinase activity in the cytosol was not stimulated, this kinase was the major kinase phosphorylating a number of the substrates and consequently had to be inhibited to prevent its masking cAMP-independent protein kinase activities. Sizable stimulations of kinase activities were then observed in extracts from progesterone-treated oocytes as compared to controls when the following substrates were utilized: Leu-Arg-Arg-Ala-Ser-Leu-Gly (Kemptide) (8-fold); the synthetic peptide, Arg-Arg-Leu-Ser-Ser-Leu-Arg-Ala, the sequence of which is based on that of a phosphorylation site in ribosomal protein S6 (8-fold); ribosomal protein S6 (8-fold); histone H1 (5-fold); skeletal muscle glycogen synthase (3-fold); and myelin basic protein (30-fold). When these substrates were used to assay extracts fractionated on DEAE-Sephacel, at least three distinct peaks of stimulated kinase activity were detected, eluting at 0.12, 0.17, and 0.21 M NaCl. These peaks were tentatively designated M-phase Activated Kinases(s), MAK-H, MAK-S, and MAK-M, respectively. Using histone H1 as a selective probe for MAK-H and S6 peptide or Kemptide as probes for MAK-S, the kinase activities comprising these peaks were found to cycle with the meiotic cell cycle.
使用了多种不同的蛋白质和肽底物来鉴定和表征非洲爪蟾卵母细胞提取物中的刺激激酶活性,这些提取物是在减数分裂细胞分裂前蛋白质磷酸化的主要爆发期制备的。虽然胞质溶胶中总的cAMP依赖性蛋白激酶活性未被刺激,但该激酶是使多种底物磷酸化的主要激酶,因此必须加以抑制以防止其掩盖cAMP非依赖性蛋白激酶活性。当使用以下底物时,与对照相比,在孕酮处理的卵母细胞提取物中观察到激酶活性有显著刺激:亮氨酸-精氨酸-精氨酸-丙氨酸-丝氨酸-亮氨酸-甘氨酸(肯普肽)(8倍);合成肽精氨酸-精氨酸-亮氨酸-丝氨酸-丝氨酸-亮氨酸-精氨酸-丙氨酸,其序列基于核糖体蛋白S6中的一个磷酸化位点(8倍);核糖体蛋白S6(8倍);组蛋白H1(5倍);骨骼肌糖原合酶(3倍);以及髓鞘碱性蛋白(30倍)。当使用这些底物分析在DEAE-葡聚糖凝胶上分级分离的提取物时,检测到至少三个不同的刺激激酶活性峰,分别在0.12、0.17和0.21 M NaCl处洗脱。这些峰分别被暂定为M期激活激酶(s)、MAK-H、MAK-S和MAK-M。使用组蛋白H1作为MAK-H的选择性探针,以及S6肽或肯普肽作为MAK-S的探针,发现构成这些峰的激酶活性随减数分裂细胞周期而循环。