Pasteurella multocida toxin: potent mitogen for cultured fibroblasts.

Pasteurella multocida toxin: potent mitogen for cultured fibroblasts.
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多杀性巴氏杆菌毒素:培养的成纤维细胞的有效有丝分裂原。

DOI:
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发表时间:
1990
影响因子:
11.1
通讯作者:
James M. Staddon
James M. Staddon
中科院分区:
综合性期刊1区
文献类型:
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作者:
Enrique Rozengurt;T. Higgins;Neil CHANTERt;Alistair J. LAXt;James M. Staddon

文献摘要

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天然多杀性巴氏杆菌毒素(PMT)被证明是Swiss 3 T3成纤维细胞的一种非常有效的促有丝分裂剂。重组PMT(rPMT)和PMT分别在1和2 pM浓度下获得DNA合成的半数最大刺激。rPMT诱导的DNA合成的程度与10%胎牛血清引起的相当,而且,在完全不存在其他因素的情况下观察到。rPMT也促进细胞增殖。该毒素也是BALB/c和NIH 3 T3细胞、3 T6细胞和第三代小鼠胚胎或人成纤维细胞的有效有丝分裂原。rPMT的促有丝分裂活性不耐热。PMT的多克隆抗血清抑制DNA合成时加入早期,但不晚,在瑞士3 T3细胞与rPMT治疗。还观察到甲胺的类似的时间依赖性作用。此外,细胞在37摄氏度而不是4摄氏度短暂暴露于rPMT,导致DNA合成的刺激。因此,毒素作用可能需要细胞进入并通过酸性隔室进行处理。毒素,在促有丝分裂浓度,导致肌醇磷酸生产的大幅增加。相反,rPMT并没有增加瑞士3 T3细胞中的环AMP的细胞内浓度。rPMT作用的基础可能提供一个独特的洞察参与细胞增殖控制的分子信号事件。
Native Pasteurella multocida toxin (PMT) is shown to be an extremely potent mitogen for Swiss 3T3 fibroblasts. Half-maximal stimulation of DNA synthesis was obtained at concentrations of 1 and 2 pM for recombinant PMT (rPMT) and PMT, respectively. The degree of rPMT-induced DNA synthesis was comparable to that elicited by 10% fetal bovine serum and, moreover, was observed in the complete absence of other factors. Cell proliferation was also enhanced by rPMT. The toxin was also a potent mitogen for BALB/c and NIH 3T3 cells, 3T6 cells, and tertiary mouse embryo or human fibroblasts. The mitogenic activity of rPMT was heat-labile. A polyclonal antiserum to PMT inhibited DNA synthesis when added early, but not late, during treatment of the Swiss 3T3 cells with rPMT. A similar time-dependent action of methylamine was also observed. Furthermore, transient exposure of the cells to rPMT at 37 degrees C, but not at 4 degrees C, resulted in a stimulation of DNA synthesis. Thus, toxin action may require cell entry and processing via an acidic compartment. The toxin, at mitogenic concentrations, caused a large increase in the production of inositol phosphates. In contrast, rPMT did not increase the intracellular concentration of cyclic AMP in Swiss 3T3 cells. The basis of rPMT action may afford a unique insight into molecular signaling events involved in the control of cell proliferation.