Levasseur S, Poleck T, Shaw M, Guinan P, Burke G
Department of Medicine, Cook County Hospital, Chicago, IL 60612.
Life Sci. 1987 Oct 5;41(14):1679-83. doi: 10.1016/0024-3205(87)90594-7.
The effects of two inhibitors of ornithine decarboxylase activity, alpha-difluoromethylornithine (DMFO) and (2R,5R) 6-heptyne-2,5 diamine (HDA), and an inhibitor of S-adenosylmethionine decarboxylase, methylglyoxal bis-guanylhydrazone (MGBG), were tested on casein kinase activity and endogenous phosphorylation in the cytosol fractions of mouse thyroid and a rat prostate tumor model, Dunning R 3327 MAT LyLu subline. When tested at 5 mM, spermine, DMFO, HDA, and MGBG stimulated mouse thyroid casein kinase activity by 230%, 14%, 65% and 106%, respectively. Similar responses were observed in prostate tumor cytosol. In mouse thyroid cytosol, spermine stimulates 32P incorporation primarily into 3 proteins (MW: 107, 88, and 56 kDa). At 5 mM, MGBG partially reproduces the effects of spermine; HDA is less effective and DMFO is without effect. Similar effects were observed on 3 proteins in prostate tumor cytosol with molecular weights of 91, 41, and 32 kDa. These data provide additional support for the hypothesis that the observed synergistic inhibitory effect of DMFO and MGBG on cell growth may not be due solely to the inhibition of polyamine biosynthesis. Our findings suggest that MGBG-mediated reduction in the phosphorylation of casein kinase substrate should be considered as one locus of action.
在小鼠甲状腺和大鼠前列腺肿瘤模型Dunning R 3327 MAT LyLu亚系的胞质溶胶组分中，测试了两种鸟氨酸脱羧酶活性抑制剂，α-二氟甲基鸟氨酸（DMFO）和（2R,5R）6-庚炔-2,5-二胺（HDA），以及一种S-腺苷甲硫氨酸脱羧酶抑制剂，甲基乙二醛双脒腙（MGBG）对酪蛋白激酶活性和内源性磷酸化的影响。当以5 mM进行测试时，精胺、DMFO、HDA和MGBG分别使小鼠甲状腺酪蛋白激酶活性提高了230%、14%、65%和106%。在前列腺肿瘤胞质溶胶中也观察到了类似的反应。在小鼠甲状腺胞质溶胶中，精胺主要刺激32P掺入3种蛋白质（分子量分别为107、88和56 kDa）。在5 mM时，MGBG部分重现了精胺的作用；HDA的效果较差，而DMFO则无作用。在前列腺肿瘤胞质溶胶中，分子量为91、41和32 kDa的3种蛋白质也观察到了类似的效果。这些数据为以下假设提供了额外的支持，即观察到的DMFO和MGBG对细胞生长的协同抑制作用可能不仅仅是由于多胺生物合成的抑制。我们的研究结果表明，MGBG介导的酪蛋白激酶底物磷酸化减少应被视为一个作用位点。
