Identification and molecular characterization of two closely related G protein-coupled receptors activated by prokineticins/endocrine gland vascular endothelial growth factor
Identification and molecular characterization of two closely related G protein-coupled receptors activated by prokineticins/endocrine gland vascular endothelial growth factor
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DOI：
10.1074/jbc.m202139200
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发表时间：
2002-05-31
影响因子：
4.8
通讯作者：
Zhou, QY
中科院分区：
文献类型：
--
作者：
Lin, DCH;Bullock, CM;Zhou, QY
我们之前描述了两种哺乳动物分泌的蛋白质，原动力蛋白1和原动力蛋白2，它们可以有效地收缩胃肠道平滑肌。原激动素1还被证明通过刺激内分泌器官来源的内皮细胞的增殖、迁移和开窗来促进血管生成。在这里，我们报道了两个密切相关的G蛋白偶联受体作为原激动素受体的克隆和特性。原激动素受体在异种系统中的表达表明，这些受体与纳摩尔浓度的重组原激动素结合并被激活。原激动素受体的激活导致钙离子的动员，刺激肌醇磷脂的周转，激活p44/p42 MAPK信号通路，这与原激动素对平滑肌收缩和血管生成的作用是一致的。MRNA表达分析表明，原运动素受体在胃肠道器官、内分泌腺和其他组织中都有表达。
We previously described two mammalian secreted proteins, prokineticin 1 and prokineticin 2, that potently contract gastrointestinal smooth muscle. Prokineticin 1 has also been shown to promote angiogenesis by stimulating proliferation, migration, and fenestration of endocrine organ-derived endothelial cells. Here we report the cloning and characterization of two closely related G protein-coupled receptors as receptors for prokineticins. Expression of prokineticin receptors in heterologous systems shows that these receptors bind to and are activated by nanomolar concentrations of recombinant prokineticins. Activation of prokineticin receptors leads to mobilization of calcium, stimulation of phosphoinositide turnover, and activation of p44/p42 MAPK signaling pathways that are consistent with the effects of prokineticins on smooth muscle contraction and angiogenesis. mRNA expression analysis reveals that prokineticin receptors are expressed in gastrointestinal organs, endocrine glands, and other tissues.