ANTHRAX TOXIN EDEMA FACTOR - A BACTERIAL ADENYLATE-CYCLASE THAT INCREASES CYCLIC-AMP CONCENTRATIONS IN EUKARYOTIC CELLS
ANTHRAX TOXIN EDEMA FACTOR - A BACTERIAL ADENYLATE-CYCLASE THAT INCREASES CYCLIC-AMP CONCENTRATIONS IN EUKARYOTIC CELLS
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DOI：
10.1073/pnas.79.10.3162
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发表时间：
1982-01-01
期刊：
影响因子：
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通讯作者：
LEPPLA, SH
中科院分区：
文献类型：
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作者：
LEPPLA, SH
炭疽毒素由3种蛋白质组成：保护性抗原（PA）、致死因子（LF）和水肿因子（EF）。这些蛋白质单独在动物中没有已知的生理作用，但成对产生2种毒性作用。PA加LF注射60 min后大鼠死亡，PA加EF注射60 min后家兔和豚鼠皮肤水肿。这些蛋白质的作用机制尚未确定。这里显示EF是由B产生的腺苷酸环化酶[ATP焦磷酸酶-裂解酶（环化），EC 4.6.1.1]。炭疽病是一种不活跃的形式。活化在与热稳定的真核细胞材料接触时发生。所得腺苷酸环化酶的比活性几乎等于已知最活跃的环化酶。在暴露于PA和EF的中国仓鼠卵巢细胞中，cAMP浓度无滞后地增加至高于正常值约200倍的值，在毒素持续存在下保持高水平，并在毒素去除后迅速下降。cAMP的增加被过量的LF完全阻断。显然，PA与细胞相互作用形成受体系统，EF和LF可能通过该受体系统进入细胞质。
Anthrax toxin is composed of 3 proteins: protective antigen (PA), lethal factor (LF) and edema factor (EF). These proteins individually cause no known physiological effects in animals but in pairs produce 2 toxic actions. Injection of PA with LF causes death of rats in 60 min, whereas PA with EF causes edema in the skin of rabbits and guinea pigs. The mechanisms of action of these proteins have not been determined. It is shown here that EF is an adenylate cyclase [ATP pyrophosphatase-lyase (cyclizing), EC 4.6.1.1] produced by B. anthracis in an inactive form. Activation occurs upon contact with a heat-stable eukaryotic cell material. The specific activity of the resulting adenylate cyclase nearly equals that of the most active known cyclase. In Chinese hamster ovary cells exposed to PA and EF, cAMP concentrations increase without a lag to values about 200-fold above normal, remain high in the continued presence of toxin and decrease rapidly after its removal. The increase in cAMP is completely blocked by excess LF. Evidently, PA interacts with cells to form a receptor system by which EF and perhaps LF gain access to the cytoplasm.