EVOLUTIONARY RELATIONSHIPS AND IMPLICATIONS FOR THE REGULATION OF PHOSPHOLIPASE-A2 FROM SNAKE-VENOM TO HUMAN SECRETED FORMS

EVOLUTIONARY RELATIONSHIPS AND IMPLICATIONS FOR THE REGULATION OF PHOSPHOLIPASE-A2 FROM SNAKE-VENOM TO HUMAN SECRETED FORMS
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DOI:
10.1007/bf02109500
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发表时间:
1990-01-01
影响因子:
3.9
通讯作者:
DENNIS, EA
DENNIS, EA
中科院分区:
生物学3区
文献类型:
--
作者:
DAVIDSON, FF;DENNIS, EA

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对40种分泌型磷脂酶A2(PLA2)的氨基酸序列进行比对,并推导出具有对应于眼镜蛇(组I)、蝰蛇(组II)和PLA2的昆虫毒液类型的三个主要分支的系统发育树。比较中的人类胰腺和最近确定的非胰腺序列分别与眼镜蛇和蝰蛇类别一致,表明在大约2亿至3亿年前爬行动物和哺乳动物分化之前,脊椎动物中至少存在两个PLA2基因。这使得第一次解决了当前PLA2进化中的主要遗传事件以及人类PLA2与蛇毒的关系,其中许多是强效毒素。哺乳动物内和细胞外PLA2的调节可能的机制的影响进行了讨论,以及有关的花生四烯酸释放,前列腺素的产生,和信号转导的控制酶的搜索问题。
The amino acid sequences of 40 secreted phospholipase A2''s (PLA2) were aligned and a phylogenetic tree derived that has three main branches corresponding to elapid (group I), viperid (group II), and insect venom types of PLA2. The human pancreatic and recently determined nonpancreatic sequences in the comparison align with the elapid and viperid categories, respectively, indicating that at least two PLA2 genes existed in the vertebrate line before the divergence of reptiles and mammals about 200-300 million years ago. This allows resolution for the first time of major genetic events in the evolution of current PLA2''s and the relationship of human PLA2''s to those of snake venom, many of which are potent toxins. Implications for possible mechanisms of regulation of mammalian intra- and extracellular PLA2''s are discussed, as well as issues relating to the search for the controlling enzymes in arachidonic acid release, prostaglandin generation, and signal transduction.