Soluble and transmembrane Isoforms of novel interleukin-17 receptor-like protein by RNA splicing and expression in prostate cancer

Soluble and transmembrane Isoforms of novel interleukin-17 receptor-like protein by RNA splicing and expression in prostate cancer
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DOI:
10.1074/jbc.m109372200
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发表时间:
2002-02-08
影响因子:
4.8
通讯作者:
Reddi, AH
Reddi, AH
中科院分区:
生物学2区
文献类型:
--
作者:
Haudenschild, D;Moseley, T;Reddi, AH

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白细胞介素-17细胞因子家族的成员存在于多种组织中(1-3),尽管创始成员白细胞介素-17仅在T细胞和B细胞中表达(4-8)。报道了一种与白细胞介素-17受体具有有限同源性的新型单程跨膜蛋白的克隆和鉴定。在前列腺、软骨、肾脏、肝脏、心脏和肌肉中检测到高mRNA水平,而在胸腺和白细胞中几乎没有检测到转录物。在人类染色体3p25.3-3p24.1的19个外显子上至少发现了11个RNA剪接变异体。通过定量逆转录酶-PCR发现不同组织中外显子的使用存在差异。预测的蛋白质范围从186到720个氨基酸。从几种剪接异构体预测缺乏跨膜和胞内结构域的可溶性分泌蛋白,并且可以通过充当可溶性诱饵受体而充当细胞因子信号传导的细胞外拮抗剂。使用针对该蛋白质的胞质和胞外结构域的抗体,我们研究了其定位,发现其在多种正常人体组织中表达,包括前列腺和前列腺癌。
Members of the interleukin-17 cytokine family are present in a variety of tissues (1-3), although the founding member, interleukin-17, is expressed exclusively in T cells and B cells (4-8). The cloning and characterization of a novel single-pass transmembrane protein with limited homology to the interleukin-17 receptor is reported. High mRNA levels were detected in prostate, cartilage, kidney, liver, heart, and muscle, whereas transcripts were barely detected in thymus and leukocytes. At least 11 RNA splice variants were found, transcribed from 19 exons on human chromosome 3p25.3-3p24.1. Differential exon usage was found in different tissues by quantitative reverse transcriptase-PCR. Predicted proteins range from 186 to 720 amino acids. Soluble secreted proteins lacking transmembrane and intracellular domains are predicted from several splice isoforms and may function as extracellular antagonists to cytokine signaling by functioning as soluble decoy receptors. Using antibodies directed at the cytoplasmic and extracellular domains of this protein, we investigated its localization and found that it was expressed in a variety of normal human tissues including prostate and in prostate cancer.