Strydom D J
BioNebraska, Inc., Lincoln 68542, USA.
Cell Mol Life Sci. 1998 Aug;54(8):811-24. doi: 10.1007/s000180050210.
The angiogenic and other biological functions of the angiogenins, members of the pancreatic RNase superfamily of proteins, are reviewed in the context of their primary and tertiary structures. The ribonucleolytic activity and interactions with the placental ribonuclease inhibitor have seen much study in the last few years. The mechanism of the angiogenic activity of angiogenin has recently been postulated as involving multiple interactions with other proteins through specific regions on the molecular surface of angiogenin. These molecular partners include heparin, plasminogen, elastase, angiostatin, actin and most importantly a 170-kilodalton receptor on subconfluent endothelial cells. The existence of the latter receptor was established in conjunction with a mitogenic activity of angiogenin on subconfluent cells. The levels of angiogenin in various physiological and disease states are summarized, including various studies on pregnancy and angiogenin. Correlations are seen between states of enhanced angiogenesis and angiogenin levels. An overview of the relationship of angiogenin and the other RNases of the superfamily showed that their genes all are in relative close proximity on human chromosome 14. Examination of the many expressed sequence tags published in the public databanks, for angiogenin and the other RNases, revealed that angiogenin and RNase-4 (the most evolutionarily conserved RNase), share various identical 5'-untranslated regions on their sets of messenger RNAs, suggesting that their genes are in very close proximity on chromosome 14 and that they are products of differential splicing. This in turn suggests that, in both humans and mice, expression of these two proteins is under identical control, with obvious implications for their biological activities. The evolutionary history of the angiogenins is examined briefly on the basis of the protein sequences of the human, rabbit, pig, two bovine and four mouse angiogenins, and two mouse angiogenin pseudogene sequences. The discrepancy between the conventional requirement for conservatism in structure to allow multimolecule interactions, and the actual fast-changing sequence of the angiogenins, in concert with the wide-ranging activity even in birds, of human angiogenin, is discussed.
本文结合血管生成素的一级和三级结构，综述了血管生成素（胰腺核糖核酸酶超家族蛋白成员）的血管生成及其他生物学功能。在过去几年中，对其核糖核酸酶活性以及与胎盘核糖核酸酶抑制剂的相互作用进行了大量研究。血管生成素血管生成活性的机制最近被推测为通过血管生成素分子表面的特定区域与其他蛋白质发生多种相互作用。这些分子伴侣包括肝素、纤溶酶原、弹性蛋白酶、血管抑素、肌动蛋白，最重要的是亚汇合内皮细胞上的一种170千道尔顿的受体。后一种受体的存在是与血管生成素对亚汇合细胞的促有丝分裂活性相关联而确定的。总结了血管生成素在各种生理和疾病状态下的水平，包括关于妊娠和血管生成素的各种研究。在血管生成增强状态与血管生成素水平之间发现了相关性。血管生成素与超家族其他核糖核酸酶关系的概述表明，它们的基因在人类14号染色体上都相对紧密相邻。对公共数据库中公布的许多血管生成素和其他核糖核酸酶的表达序列标签进行检查发现，血管生成素和核糖核酸酶 - 4（进化上最保守的核糖核酸酶）在其信使核糖核酸组上共享各种相同的5' - 非翻译区，这表明它们的基因在14号染色体上非常紧密相邻，并且它们是可变剪接的产物。这反过来表明，在人类和小鼠中，这两种蛋白质的表达受相同控制，这对它们的生物学活性具有明显影响。基于人类、兔子、猪、两种牛和四种小鼠血管生成素的蛋白质序列以及两种小鼠血管生成素假基因序列，简要研究了血管生成素的进化历史。讨论了传统上对结构保守性以允许多分子相互作用的要求与血管生成素实际快速变化的序列之间的差异，以及即使在鸟类中人类血管生成素仍具有广泛活性的情况。
