Human transforming growth factor-β activates a receptor serine/threonine kinase from the intravascular parasite Schistosoma mansoni
Human transforming growth factor-β activates a receptor serine/threonine kinase from the intravascular parasite Schistosoma mansoni
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DOI：
10.1074/jbc.m104685200
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发表时间：
2001-08-24
影响因子：
4.8
通讯作者：
Pearce, EJ
中科院分区：
文献类型：
--
作者：
Beall, MJ;Pearce, EJ
Helminth寄生虫血吸虫Mansoni的生物学与其哺乳动物宿主的生物学紧密融合。 SMRK1是一种不同的配体特异性的I型I型转化生长因子β（TGF-BETA）受体，以前被确定为允许血吸虫对宿主衍生生长因子反应的受体的候选者。 TGF-β家族包括激活素，骨形态发生蛋白（BMP）和TGF-β，所有这些都可以在后生动物发育中起着至关重要的作用。对TGF-β和激活素反应的受体的下游信号蛋白是SMAD2，而通过SMAD1对BMPS信号响应的受体。当SMAD1（SMSMAD1）或SMSMAD2的组成型活性突变体过表达时，SMSMAD磷酸化的受体依赖性调节和仅使用SMSMAD2的受体依赖性调节发生。为了评估SMRK1的潜在配体激活剂，该嵌合体受到SMRK1的细胞外结构域的嵌合受体。使用人类I型TGF-β受体的LAR结构域。嵌合受体结合的放射性标记的TGF-β，可以激活荧光素酶报告基因，以响应TGF-BETA1和TGF-BETA3，而不是BMP7。使用全长SMRK1获得了确认结果。这些实验暗示TGF-beta是SMRK1的配体，也是寄生虫生长和发育的潜在宿主调节剂。
The biology of the helminth parasite Schistosoma mansoni is closely integrated with that of its mammalian host. SmRK1, a divergent type I transforming growth factor-beta (TGF-beta) receptor of unknown ligand specificity, was previously identified as a candidate for a receptor that allows schistosomes to respond to host-derived growth factors. The TGF-beta family includes activin, bone morphogenetic proteins (BMPs), and TGF-beta, all of which can play crucial roles in metazoan development. The downstream signaling protein of receptors that respond to TGF-beta and activin is Smad2, whereas the receptors that respond to BMPs signal via Smad1. When a constitutively active mutant of SmRK1 was overexpressed with either schistosome Smad1 (SmSmad1) or SmSmad2, a receptor-dependent modulation of SmSmad phosphorylation and luciferase reporter activity occurred only with SmSmad2. To evaluate potential ligand activators of SmRK1, a chimeric receptor containing the extracellular domain of SmRK1 joined to the intracellular. lar domain of the human type I TGF-beta receptor was used. The chimeric receptor bound radiolabeled TGF-beta and could activate a luciferase reporter gene in response to both TGF-beta1 and TGF-beta3 but not BMP7. Confirmatory results were obtained using full-length SmRK1. These experiments implicate TGF-beta as a ligand for SmRK1 and as a potential host-derived regulator of parasite growth and development.