Polyamines inhibit phospholipid-sensitive and calmodulin-sensitive Ca2+-dependent protein kinases.
Polyamines inhibit phospholipid-sensitive and calmodulin-sensitive Ca2+-dependent protein kinases.
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多胺抑制磷脂敏感和钙调蛋白敏感的 Ca2 依赖性蛋白激酶。
DOI：
10.1042/bj2130281
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Kuo,JF
中科院分区：
文献类型：
--
作者：
Qi,DF;Schatzman,RC;Mazzei,GJ;Turner,RS;Raynor,RL;Liao,S;Kuo,JF
研究了多胺对各种蛋白激酶的影响。结果表明，多胺对磷脂敏感的Ca ~（2+）依赖性蛋白激酶和肌球蛋白轻链激酶（Ca ~（2+）依赖性蛋白激酶中的一种钙调素敏感的蛋白激酶）均有不同程度的抑制作用，其抑制效果的近似顺序为精胺= 1，12-十二烷二胺大于亚精胺= 1，10-癸烷二胺，远大于尸胺=腐胺。动力学分析表明，精胺抑制磷脂敏感酶非竞争性相对于钙（Ki = 0.84 mM）和磷脂酰丝氨酸（Ki = 0.90 mM），它也抑制肌球蛋白轻链激酶非竞争性相对于钙（Ki = 1.82 mM）和钙调蛋白（Ki = 2.73 mM）。相比之下，1，12-二氨基十二烷竞争性抑制磷脂敏感性酶相对于Ca 2+（Ki = 0.45 mM）和磷脂酰丝氨酸（Ki = 0.50 mM），它也抑制肌球蛋白轻链激酶竞争性相对于钙调蛋白（Ki = 0.63 mM），但非竞争性相对于Ca 2+（Ki = 1.49 mM）。此外，精胺（0.5 mM）被发现显着抑制磷脂酰丝氨酸/Ca 2+和钙调素/Ca 2+刺激的内源性蛋白质在大鼠脑颗粒部分的磷酸化。所有测试的多胺几乎没有影响环AMP依赖性和环GMP依赖性蛋白激酶。研究发现，与精胺一样，聚精氨酸是Ca 2+依赖性蛋白激酶的更有选择性的抑制剂，而聚谷氨酸则优先抑制环核苷酸依赖性酶。目前的结果表明，除了某些亲脂性化合物（如三氟拉嗪，棕榈酰肉毒碱，阿霉素和萘磺酰胺）和多肽与疏水区（如蜂毒肽和多粘菌素B）先前报道，聚阳离子化合物（以多胺为例）也可以抑制两类钙依赖性蛋白激酶需要磷脂或钙调素作为辅因子。由于高细胞浓度（高达10 mM）和多胺的差异效应，有人建议，精胺，并在较小程度上亚精胺和腐胺，可能参与某些钙依赖性蛋白磷酸化系统在体内的调节。
Effects of polyamines on various protein kinases were investigated. It was found that both phospholipid-sensitive Ca2+-dependent protein kinase and myosin light-chain kinase (a calmodulin-sensitive species of Ca2+-dependent protein kinase) were inhibited to different degrees by polyamines, with an approximate order of inhibitory potency of spermine = 1, 12-diaminododecane greater than spermidine = 1, 10-diaminodecane much greater than cadaverine = putrescine. Kinetic analysis revealed that spermine inhibited the phospholipid-sensitive enzyme non-competitively with respect to Ca2+ (Ki = 0.84 mM) and phosphatidylserine (Ki = 0.90 mM); it also inhibited myosin light-chain kinase non-competitively with respect to Ca2+ (Ki = 1.82 mM) and calmodulin (Ki = 2.73 mM). 1, 12-Diaminododecane, in comparison, inhibited the phospholipid-sensitive enzyme competitively with respect to Ca2+ (Ki = 0.45 mM) and phosphatidylserine (Ki = 0.50 mM); it also inhibited myosin light-chain kinase competitively with respect to calmodulin (Ki = 0.63 mM) but non-competitively with respect to Ca2+ (Ki = 1.49 mM). Moreover, spermine (0.5 mM) was found to inhibit markedly phosphatidylserine/Ca2+- and calmodulin/Ca2+-stimulated phosphorylation of endogenous proteins in rat brain particulate fraction. All the polyamines tested were practically without effect on cyclic AMP-dependent and cyclic GMP-dependent protein kinases. Polyarginine, like spermine, was found to be a more selective inhibitor of Ca2+-dependent protein kinases, whereas polyglutamate preferentially inhibited the cyclic nucleotide-dependent enzymes. The present results indicated that, in addition to certain lipophilic compounds (such as trifluoperazine, palmitoylcarnitine, adriamycin and naphthalenesulphonamide) and polypeptides with hydrophobic regions (such as melittin and polymyxin B) previously reported, polycationic compounds (exemplified by polyamines) could also inhibit the two classes of Ca2+-dependent protein kinases requiring either phospholipid or calmodulin as a cofactor. Because of the high cellular concentration (up to 10 mM) and the differential effects of polyamines, it is suggested that spermine, and to smaller extents spermidine and putrescine, may be involved in the regulation of certain Ca2+-dependent protein-phosphorylation systems in vivo.