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首页> 外文期刊>American Journal of Physiology >Pertussis toxin directly activates endothelial cell p42/p44 MAP kinases via a novel signaling pathway.
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Pertussis toxin directly activates endothelial cell p42/p44 MAP kinases via a novel signaling pathway.

机译：百日咳毒素通过新的信号通路直接激活内皮细胞p42 / p44 MAP激酶。

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摘要

Bordetella pertussis generates a bacterial toxin utilized in signal transduction investigation because of its ability to ADP ribosylate specific G proteins. We previously noted that pertussis toxin (PTX) directly activates endothelial cells, resulting in disruption of monolayer integrity and intercellular gap formation via a signaling pathway that involves protein kinase C (PKC). We studied the effect of PTX on the activity of the 42- and 44-kDa extracellular signal-regulated kinases (ERK), members of a kinase family known to be activated by PKC. PTX caused a rapid time-dependent increase in bovine pulmonary artery endothelial cell ERK activity that was significantly attenuated by 1) pharmacological inhibition of MEK, the upstream ERK activating kinase, 2) an MEK dominant-negative construct, and 3) PKC inhibition with bisindolylmaleimide. There was little evidence for the involvement of either Gbetagamma-subunits, Ras GTPases, Raf-1, p60(src), or phosphatidylinositol 3'-kinases in PTX-mediated ERK activation. Both the purified beta-oligomer binding subunit of the PTX holotoxin and a PTX holotoxin mutant genetically engineered to eliminate intrinsic ADP ribosyltransferase activity completely reproduced PTX effects on ERK activation, suggesting that PTX-induced ERK activation involves a novel PKC-dependent signaling mechanism that is independent of either Ras or Raf-1 activities and does not require G protein ADP ribosylation.
机译：百日咳博德特氏菌产生一种细菌毒素，可用于信号转导研究，因为它具有ADP核糖基化特定G蛋白的能力。我们以前注意到百日咳毒素（PTX）直接激活内皮细胞，导致单层完整性的破坏和细胞间间隙的形成通过涉及蛋白激酶C（PKC）的信号传导途径。我们研究了PTX对42 kDa和44 kDa细胞外信号调节激酶（ERK）的活性的作用，ERK是已知由PKC激活的激酶家族的成员。 PTX引起牛肺动脉内皮细胞ERK活性快速的时间依赖性增加，该活性被1）MEK，上游ERK活化激酶的药理抑制作用，2）MEK显性负性构建物和3）bisindolylmaleimide的PKC抑制作用显着减弱。几乎没有证据表明Gbetagamma亚基，Ras GTPases，Raf-1，p60（src）或磷脂酰肌醇3'激酶参与PTX介导的ERK激活。 PTX holotoxin的纯化的β-低聚物结合亚基和经过基因工程改造以消除固有的ADP核糖基转移酶活性的PTX holotoxin突变体均完全重现了PTX对ERK激活的作用，这表明PTX诱导的ERK激活涉及一种新的PKC依赖性信号传导机制，即与Ras或Raf-1活性无关，并且不需要G蛋白ADP核糖基化。

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