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The oxytocinase subfamily of M1 aminopeptidases

M1 氨肽酶催产素亚家族

基本信息

批准号：
15390032
负责人：
TSUJIMOTO Masafumi
金额：
$ 9.73万
依托单位：
RIKEN
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

In our previous works, we identified and cloned two aminopeptidases (P-LAP and A-LAP) as novel enzymes belonging to the M1 family of aminopeptidases. In addition, we showed that A-LAP is a final processing enzyme of peptide antigens presented to MHC class I molecules in the endoplasmic reticulum (ER). Based on these results, we further examined the structural and functional analyses of M1 family members in this study and we identified one novel aminopeptidase. In addition, we have performed the functional analyses of these three enzymes that we have identified.By searching a database, we have identified and cloned a novel protein designated as leukocyte-derived arginine aminopeptidase (L-RAP). Since L-RAP is homologous to P-LAP and A-LAP, we are now proposing that these three enzymes should be classified into "The oxytocinase subfamily of M1 aminopeptidases".Functional analyses of P-LAP indicated that after treatment of renal-derived NRK52E cells with vasopressin, rapid translocation of P-LAP from intracellular vesicles to plasma membranes was observed. Since vasopressin is a good substrate of the enzyme, these results suggest the existence of the P-LAP-mediated negative feedback mechanism of vasopressin action in the kidney.As for A-LAP, we have analyzed its ER-retention mechanism and found a protein binding to the enzyme. Since this protein contains an ER-retention signal (HDEL) in its C-terminal end, it is plausible that A-LAP is retained in the ER via binding to the protein. Based on this result, we will further examine the total aspect of the ER-retention mechanism of the enzyme.It was also found that L-RAP is localized in the luminal side of the ER and can process N-extended precursor peptide antigens presented to the MHC class I molecules to mature forms. These results indicate for the first time that L-RAP is the second ER-aminopeptidase that can trim N-extended precursors to antigenic peptides.

在我们以前的工作中，我们确定并克隆了两个氨肽酶（P-peptidase和A-peptidase）作为新的酶属于M1家族的氨肽酶。此外，我们发现，A-β是一个最终的加工酶的肽抗原提出的MHC I类分子在内质网（ER）。基于这些结果，我们进一步研究了M1家族成员的结构和功能分析，在这项研究中，我们确定了一个新的氨肽酶。此外，我们对这三种酶进行了功能分析，并通过数据库检索，鉴定和克隆了一种新的蛋白质，命名为白细胞衍生的精氨酸氨肽酶（L-RAP）。由于L-RAP与P-RAP和A-RAP同源，我们建议将这三种酶归入“M1氨基肽酶的催产素亚家族”。P-RAP的功能分析表明，在用加压素处理肾源性NRK 52 E细胞后，观察到P-RAP从细胞内囊泡快速移位到质膜。由于加压素是该酶的良好底物，这些结果提示加压素在肾脏中作用的负反馈机制的存在。由于该蛋白质在其C-末端含有ER-滞留信号（HDEL），因此可能的是，A-binding通过与蛋白质结合而保留在ER中。基于这一结果，我们将进一步研究酶的ER保留机制的整体方面。还发现L-RAP定位于ER的腔侧，并且可以将呈递给MHC I类分子的N-延伸前体肽抗原加工成成熟形式。这些结果首次表明，L-RAP是第二个ER-氨基肽酶，可以修剪N-延伸的抗原肽的前体。

项目成果

期刊论文数量（39）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Distribution of Adipocyte-derived leucine aminopeptidase (A-LAP)/ER-aminopeptidase(ERAP)-1 in human uterine endometrium

脂肪细胞来源的亮氨酸氨肽酶(A-LAP)/ER-氨肽酶(ERAP)-1在人子宫内膜中的分布

DOI：
发表时间：
2004
期刊：
Journal of Histochemistry and Cytochemistry 52
影响因子：
0
作者：
Okamoto;K;Kashima;K;Pereg;Y;Ishida;M;Yamazaki;S.Nota;A;Teunisse;A;Migliorini;D;Kitabayashi;I;Marine;JC;Prives;C;Shiloh;Y;Jochemsen;AG;Taya;Y.;H.Tamamura;Shibata D. et al.
通讯作者：
Shibata D. et al.

Ino K.et al.: "Expression of placental leucine aminopeptidase and adipocyte-derived leucine aminopeptidase in human normal and malignant invasive trophoblastic cells."Laboratory Investigation. 73. 1799-1810 (2003)

Ino K.等人：“胎盘亮氨酸氨肽酶和脂肪细胞来源的亮氨酸氨肽酶在人类正常和恶性侵袭性滋养层细胞中的表达。”实验室研究。