Analyses of the glycan structure of which Klotho recognizes
Analyses of the glycan structure of which Klotho recognizes
批准号:
21390058
负责人:
IMURA Akihiko
金额:
$11.32万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2010
资助国家:
日本
项目状态:
已结题
起止时间:
2010 至 2011
中文摘要
β-Klotho是一种I型单跨膜蛋白,具有两个串联的糖苷酶样域,主要在肝细胞中表达。该基因,β-Klotho和α-Klotho属于Klotho家族。FGF19被认为是一种脂质介体,它控制胆汁酸的合成来调节脂质的摄入。FGF19蛋白在回肠中表达,在肝脏中输入信号。β-Klotho的表达是信号所必需的。像α-Klotho一样,β-Klotho也识别单糖。因此,我们推测该单糖结合在FGF19蛋白上。使用独特的糖链抗体,我们已经确定了β-Klotho识别的特定糖链。我们的研究揭示了这些Klotho凝集素是如何转导成纤维细胞生长因子信号的。此外,我们还证明了α-Klotho通过相同的识别系统与NAK-ATPase结合。同时,了解了一种蛋白质如何与不同的结合伙伴,如成纤维细胞生长因子家族和NAK-ATPase复合体结合,我们的理解将导致解决生理蛋白质,如NAK-ATPase复合体如何被招募到表膜上的悬而未决的问题。也就是说,可以理解的是,几种糖基转移酶对糖基化的调节调节了生理分子的运输。应该预计,更广泛的研究将会扩大,以揭示多糖的生物学意义。
英文摘要
Beta-Klotho, a type-I single-spanning membrane protein, has two tandem glycosidase-like domains and is expressed mainly in hepatocyte. The gene, beta-klotho, and alpha-Klotho belong to the Klotho family.FGF19 was identified as a lipid mediator ; which controls bile acids synthesis to regulate lipid intake. The FGF19 protein is expressed in ileum to input signal in liver. Expression of the beta-Klotho is necessary for the signal.Like alpha-Klotho, beta-Klotho recognizes a monosaccharide as well. Therefore, we deduced that the monosaccharide is attached to FGF19 protein. Using an antibody for unique glycan, we have identified the specific glycan of which beta-Klotho recognizes.Our study revealed how these Klotho lectins transduces the FGF signals. Furthermore, we have shown that alpha-Klotho binds to NaK-ATPase through the same recognition system. Meanwhile, it has been understood how one protein can bind to distinct binding partners, FGF family and NaK-ATPase complex.Our understandings will lead to solve unsolved questions that how physiological proteins, such as NaK-ATPase complex, are recruited to the surface membrane. That is, it would be understood that regulation of glycosylation by several glycosyl transferases regulates transports of the physiological molecules. It should be expected that more wide study to reveal biological significance of glycan would spread.
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DOI:
--
发表时间:
2011
期刊:
実験医学
影响因子:
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DOI:
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发表时间:
2011
期刊:
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DOI:
10.1016/j.bbrc.2010.06.110
发表时间:
2010-07-30
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
影响因子:
3.1
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DOI:
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发表时间:
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DOI:
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发表时间:
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期刊:
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