Pasteurella multocida toxin selectively facilitates phosphatidylinositol 4,5-bisphosphate hydrolysis by bombesin, vasopressin, and endothelin. Requirement for a functional G protein.
Pasteurella multocida toxin selectively facilitates phosphatidylinositol 4,5-bisphosphate hydrolysis by bombesin, vasopressin, and endothelin. Requirement for a functional G protein.
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多杀性巴氏杆菌毒素选择性地促进铃蟾肽、加压素和内皮素水解磷脂酰肌醇 4,5-二磷酸。
DOI：
10.1016/s0021-9258(19)74039-3
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Enrique Rozengurt
中科院分区：
文献类型：
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作者：
Anne C. Murphy;Enrique Rozengurt
用亚饱和浓度的重组多杀性巴氏杆菌毒素（rPMT）处理瑞士3 T3细胞，显著增强蛙皮素、加压素和内皮素诱导的磷酸肌醇的产生，但血小板源性生长因子（PDGF）（AA和BB同源二聚体）不诱导。同样，神经肽，但不是PDGF引起的转移，在剂量依赖性增加肌醇磷酸诱导的rPMT。蛙皮素诱导的肌醇磷酸的积累率增加2倍，而PDGF的rPMT治疗不受影响。rPMT处理也增强蛙皮素诱导的肌醇（1，4，5）三磷酸，磷脂酰肌醇4，5-二磷酸水解的直接产物。相反，用rPMT处理细胞对磷脂酶C γ的酪氨酸磷酸化没有影响。蛋白激酶C的耗竭增加rPMT诱导的肌醇磷酸的方式类似于蛙皮素，但不是PDGF。因此，rPMT选择性地增强神经肽介导的磷酸肌醇的产生。rPMT对磷脂酰肌醇4，5-二磷酸水解的作用持续存在于链球菌溶血素O-透化细胞中。鸟苷5 '-O-（β-硫代二磷酸）透化细胞的添加显着减少rPMT诱导的肌醇磷酸在时间和剂量依赖性的方式。rPMT还增加磷脂酶C对游离钙的敏感性。我们的结果强烈地表明rPMT的作用促进G蛋白与磷脂酶C的偶联。
Treatment of Swiss 3T3 cells with a subsaturating concentration of recombinant Pasteurella multocida toxin (rPMT) markedly potentiated the production of inositol phosphates induced by bombesin, vasopressin, and endothelin but not by platelet-derived growth factor (PDGF) (AA and BB homodimers). Similarly, the neuropeptides but not PDGF caused a shift in the dose-dependent increase in inositol phosphates induced by rPMT. The rate of accumulation of inositol phosphates induced by bombesin was increased 2-fold by rPMT treatment while that of PDGF was unaffected. rPMT treatment also enhanced bombesin-induced inositol(1,4,5)trisphosphate, the direct product of phosphatidylinositol 4,5-bisphosphate hydrolysis. In contrast, treatment of cells with rPMT had no effect on the tyrosine phosphorylation of phospholipase C gamma. Depletion of protein kinase C increased rPMT-induced inositol phosphates in a manner similar to that observed for bombesin but not PDGF. Thus, rPMT selectively potentiates neuropeptide-mediated inositol phosphate production. The action of rPMT on phosphatidylinositol 4,5-bisphosphate hydrolysis persisted in streptolysin O-permeabilized cells. Addition of guanosine 5'-O-(beta-thiodiphosphate) to permeabilized cells markedly reduced rPMT-induced inositol phosphates in a time- and dose-dependent manner. rPMT also increased the sensitivity of phospholipase C for free calcium. Our results strongly suggest that the action of rPMT facilitates the coupling of G protein to phospholipase C.