Prepens U, Just I, Hofmann F, Aktories K
Institut für Pharmakologie und Toxikologie, Albert-Ludwigs-Universiät, Freiburg, Germany.
Adv Exp Med Biol. 1997;419:349-53. doi: 10.1007/978-1-4419-8632-0_46.
The influence of different ADP-ribosylating and glucosylating cytotoxins on stimulated protein tyrosine phosphorylation and secretion in rat basophilic leukemia (RBL) cells was studied. Treatment of RBL cells with Clostridium botulinum C2 toxin, which specifically ADP-ribosylated monomeric G-actin and caused complete depolymerization of the actin cytoskeleton in intact cells, inhibited Fc epsilon RI receptor-mediated tyrosine phosphorylation of various proteins in a time- and concentration-dependent manner with maximal effects at 100 ng/ml C2I and 200 ng/ml C2I. C2 toxin (10 ng/ml C2I and 20 ng/ml C2II) increased antigen- or calcium ionophore (A23187)-stimulated [3H]serotonin release maximally by about 3 fold. Clostridium botulinum C3, which ADP-ribosylated Rho in intact RBL cells, had no effect on protein tyrosine phosphorylation and stimulated secretion. In contrast, the cytotoxic Clostridium difficile toxin B (ToxB), which glucosylated the Rho-subtype family members RhoA and Cdc42, blocked or reduced antigen- or calcium ionophore-mediated [3H]serotonin release, respectively, and decreased tyrosine phosphorylation of a 110 kDa protein. The data indicate that different actin pools control tyrosine phosphorylation and secretion in RBL cells and suggest that Rho subfamily proteins regulate secretion independently of the actin cytoskeleton.
研究了不同的ADP-核糖基化和糖基化细胞毒素对大鼠嗜碱性白血病（RBL）细胞中刺激的蛋白酪氨酸磷酸化和分泌的影响。用肉毒杆菌C2毒素处理RBL细胞，该毒素特异性地ADP-核糖基化单体G-肌动蛋白并导致完整细胞中肌动蛋白细胞骨架完全解聚，以时间和浓度依赖性方式抑制FcεRI受体介导的各种蛋白的酪氨酸磷酸化，在100 ng/ml C2I和200 ng/ml C2I时效果最佳。C2毒素（10 ng/ml C2I和20 ng/ml C2II）使抗原或钙离子载体（A23187）刺激的[3H]5-羟色胺释放最大增加约3倍。在完整的RBL细胞中ADP-核糖基化Rho的肉毒杆菌C3对蛋白酪氨酸磷酸化和刺激的分泌没有影响。相反，细胞毒性艰难梭菌毒素B（ToxB）使Rho亚型家族成员RhoA和Cdc42糖基化，分别阻断或减少抗原或钙离子载体介导的[3H]5-羟色胺释放，并降低110 kDa蛋白的酪氨酸磷酸化。数据表明不同的肌动蛋白池控制RBL细胞中的酪氨酸磷酸化和分泌，并表明Rho亚家族蛋白独立于肌动蛋白细胞骨架调节分泌。
