SRPX2 is a novel chondroitin sulfate proteoglycan that is overexpressed in gastrointestinal cancer.

SRPX2 is a novel chondroitin sulfate proteoglycan that is overexpressed in gastrointestinal cancer.
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DOI:
10.1371/journal.pone.0027922
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Nishio K
Nishio K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tanaka K;Arao T;Tamura D;Aomatsu K;Furuta K;Matsumoto K;Kaneda H;Kudo K;Fujita Y;Kimura H;Yanagihara K;Yamada Y;Okamoto I;Nakagawa K;Nishio K

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SRPX2 (Sushi repeat-containing protein, X-linked 2)最近作为一种多功能蛋白出现,参与癫痫、血管生成和细胞粘附。在这里,我们对这种蛋白质进行了生化分析。SRPX2蛋白经高度翻译后修饰后分泌。软骨素酶ABC处理使纯化的SRPX2蛋白的分子质量完全降低到预期的大小,而肝素酶、角化酶和透明蛋白酶则没有。用抗硫酸软骨素抗体检测分泌的SRPX2蛋白。这些结果表明SRPX2是一种新型硫酸软骨素蛋白多糖(CSPG)。此外,结合实验显示肝细胞生长因子以剂量依赖性结合SRPX2蛋白,并且推测配体-糖胺聚糖可能在蛋白聚糖中相互作用。就其分子结构而言,SRPX2具有与其他四种CSPGs/ ecticans相似的寿司重复模块;然而,SRPX2的分子结构似乎与电子分子有很大的不同。综上所述,我们发现SRPX2是一种在胃肠道癌细胞中过表达的新型CSPG。我们的研究结果提供了SRPX2在癌细胞中的关键糖生物学见解,并证明SRPX2是癌症相关蛋白多糖家族的新成员。
SRPX2 (Sushi repeat-containing protein, X-linked 2) has recently emerged as a multifunctional protein that is involved in seizure disorders, angiogenesis and cellular adhesion. Here, we analyzed this protein biochemically. SRPX2 protein was secreted with a highly posttranslational modification. Chondroitinase ABC treatment completely decreased the molecular mass of purified SRPX2 protein to its predicted size, whereas heparitinase, keratanase and hyaluroinidase did not. Secreted SRPX2 protein was also detected using an anti-chondroitin sulfate antibody. These results indicate that SRPX2 is a novel chondroitin sulfate proteoglycan (CSPG). Furthermore, a binding assay revealed that hepatocyte growth factor dose-dependently binds to SRPX2 protein, and a ligand-glycosaminoglycans interaction was speculated to be likely in proteoglycans. Regarding its molecular architecture, SRPX2 has sushi repeat modules similar to four other CSPGs/lecticans; however, the molecular architecture of SRPX2 seems to be quite different from that of the lecticans. Taken together, we found that SRPX2 is a novel CSPG that is overexpressed in gastrointestinal cancer cells. Our findings provide key glycobiological insight into SRPX2 in cancer cells and demonstrate that SRPX2 is a new member of the cancer-related proteoglycan family.
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