Conservation of a platelet activating domain of Aggrus/podoplanin as a platelet aggregation-inducing factor
Conservation of a platelet activating domain of Aggrus/podoplanin as a platelet aggregation-inducing factor
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DOI：
10.1016/j.gene.2006.04.023
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发表时间：
2006-08-15
期刊：
影响因子：
3.5
通讯作者：
Osawa, Motoki
中科院分区：
文献类型：
--
作者：
Kaneko, Mika Kato;Kato, Yukinari;Osawa, Motoki
人aggrus/podoplan in是一种已知的癌细胞的血小板聚集诱导因子，也被认为是淋巴管内皮细胞的特异性标志物。已知人类Aggrus在精原细胞瘤、鳞癌、恶性间皮瘤、肉瘤和几种脑肿瘤中都有表达。在我们以前的研究中，在糖基化缺陷的中国仓鼠卵巢(CHO)细胞系的实验中，人和小鼠Aggrus的唾液酸化O-聚糖被证明是其诱导血小板聚集活性的关键。我们新克隆了来自大鼠、仓鼠、狗和牛的Aggrus同源物，以及人和小鼠的cDNA，并证实了Aggrus中存在三个串联重复的血小板聚集刺激(Plag)结构域，它们在所有同源物中都是保守的。我们发现牛Aggrus在第一个Plag结构域有一个零星的缺失突变，并且缺乏诱导血小板聚集的活性。我们在Aggrus的Plag结构域中引入了点突变，并表明第一个或最后一个Plag结构域对活性至关重要，但不是中间结构域。此外，我们还研究了Aggrus的Plag结构域的分子进化过程。在鸟类和哺乳动物分化之后，出现了Plag结构域及其活性。总之，我们提供的证据表明，Aggnis同源物保守了EDxxVTPG胞外区的片段，这是其诱导血小板聚集活性的关键。(C)2006爱思唯尔B.V.保留所有权利。
Human Aggrus/podoplanin is an identified platelet aggregation-inducing factor of cancer cells, which is also known as a specific marker of lymphatic endothelium. Human Aggrus was known to be expressed in seminoma, squamous cell carcinoma, malignant mesothelioma, sarcomas and several brain tumors. In our previous studies, the sialylated O-glycan of human and mouse Aggrus were shown to be critical for its platelet aggregation-inducing activity in the experiments using the glycosylation-deficient Chinese hamster ovary (CHO) cell lines. We newly cloned Aggrus homologues from rat, hamster, dog and bovine cDNAs, in addition to the human and mouse CDNAs, and confirmed there are three tandem repeats of the platelet aggregation-stimulating (PLAG) domain in Aggrus, which were conserved in all homologues. We found that bovine Aggrus has a sporadic deletion mutation in the first PLAG domain, and lacks platelet aggregation-inducing activity. We introduced point mutation in the PLAG domain of Aggrus and showed that either the first or last PLAG domain is critical for activity, but not the middle domain. In addition, we studied the molecular evolutionary process of the PLAG domain of Aggrus. The PLAG domain and its activity appeared after the divergence of avians and mammals. In conclusion, we provide evidence that Aggnis homologues conserved the segment of EDxxVTPG in their extracellular domain which are critical for their platelet aggregation-inducing activities. (c) 2006 Elsevier B.V. All rights reserved.