Aminopeptidase A in human placenta

Mizutani, Shigehiko; Okano, Kikumi; Hasegawa, Eiji; Sakura, Harutake; Yamada, Masaaki

doi:10.1016/0005-2744(81)90240-0

Cited by 56 publications

(32 citation statements)

References 15 publications

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“…Purification of APA to homogeneity with these tissue sources is complicated by the relative abundance of other structurally related enzymes and lack of a specific antibody (19,20,(22)(23)(24)(25). The relatively high expression levels of the BP-1/6C3 antigen on transformed pre-B cells has allowed its purification, sequence analysis, and cDNA cloning (11).…”

Section: Discussionmentioning

confidence: 99%

Aminopeptidase A activity of the murine B-lymphocyte differentiation antigen BP-1/6C3.

Cooper

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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The predicted amino acid sequence of the cDNA encoding the murine B-lymphocyte differentiation antigen BP-1/6C3 suggested that it is a member of the zincdependent metalloprotease family, possibly an aminopeptidase related to aminopeptidase N [microsomal aminopeptidase; a-aminoacyl-peptide hydrolase (microsomal), EC 3. (refs. 4-6; unpublished results).While its broad tissue distribution implied diverse biological function, studies of the BP-1/6C3 antigen thus far have been focused mainly on its possible role in B lymphocyte development. The BP-1/6C3 molecule is expressed on pre-B and immature B-lineage cells in the bone marrow (2, 3, 7), and its expression on stromal cell lines correlates with their ability to support pre-B-cell growth (4). Moreover, interleukin 7 (IL-7) preferentially induces BP-1/6C3 expression together with pre-B-cell proliferation (6, 8) and up-regulated expression of the BP-1/6C3 antigen, which is often seen on transformed pre-B cells (1, 2, 9, 10).In an effort to define the structure and function of this interesting cell-surface molecule, we purified the antigen and cloned its cDNA from an Abelson murine leukemia virustransformed pre-B-cell line (11). The amino acid sequence predicted from the cDNA sequence suggested that the murine BP-1/6C3 antigen is a member of the zinc-dependent metalloprotease family, possibly an aminopeptidase related to aminopeptidase N [APN; microsomal aminopeptidase; a-aminoacyl-peptide hydrolase (microsomal) EC 3.4.11.2]. Four distinctive types of aminopeptidases have been reported (12). These include APN, which has a relatively broad specificity acting on peptides with an N-terminal neutral amino acid; aminopeptidase A [APA; u-a-aspartyl(L-a-glutamyl)-peptide hydrolase, EC 3.4.11.7], acting on peptides with N-terminal acidic amino acids; aminopeptidase P (aminoacrylprolyl-peptide hydrolase, EC 3.4.11.9) and aminopeptidase W, which hydrolyze peptides in which the penultimate amino acid is a proline or a tryptophan.In the present studies, we have obtained evidence that the BP-1/6C3-reactive molecule exhibits APA activity.

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Section: Discussionmentioning

confidence: 99%

Aminopeptidase A activity of the murine B-lymphocyte differentiation antigen BP-1/6C3.

Cooper

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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“…The enzyme has been purified from human placenta and pregnancy serum. It is present in various reproductive organs (63,70,71). The relative molecular mass of the human serum enzyme has been estimated as 260000.…”

Section: Aminopeptidase Amentioning

confidence: 99%

Human Aminopeptidases: A Review of the Literature

Sanderink¹,

Artur²,

Siest³

1988

Clinical Chemistry and Laboratory Medicine

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Summary:The aminopeptidases constitute a group of enzymes with closely related activities. In clinical chemistry the analysis of the aminopeptidases and of their multiple forms in serum has for a long time been hindered by considerable confusion concerning their identification, and by a lack of characterization. This is in part due to the often large, and sometimes overlapping substrate specificities of the aminopeptidases. This paper reviews the biochemical properties of the different aminopeptidases, the specificities of the assays used for their analysis in serum, some aspects of their multiple forms -which are especially known to occur for alanine äminopeptidase (EC 3.4.11.2) -and the importance of the determination of aminopeptidases and their multiple forms in clinical chemistry.

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“…15 We purified APA from the human placenta 16 and demonstrated the role of this enzyme in regulating blood pressure during pregnancy. 17 However, there have been few reports on APA expression and its functional significance in tumor cells.…”

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confidence: 99%

Regulation of aminopeptidase A expression in cervical carcinoma: role of tumor–stromal interaction and vascular endothelial growth factor

Suganuma

Ino

Shibata

et al. 2004

Laboratory Investigation

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We previously demonstrated that aminopeptidase A (APA), a membrane-bound metallopeptidase degrading bioactive peptides such as angiotensin II (Ang II), is expressed in neoplastic lesions of the uterine cervix, and that its expression is upregulated as the lesion progresses from cervical intraepithelial neoplasms (CIN) toward invasive squamous cell carcinomas (SCC). The present study investigated the regulatory mechanisms involved in APA expression and its potential role in cervical carcinoma. Immunohistochemical staining in high-grade CIN and SCC tissues showed that APA was strongly expressed at the edge of lesions adjacent to cervical stromal cells. Fluorescence-activated cell sorting analysis demonstrated that cell surface APA expression was extremely low in three human SCC cell lines, SiHa, TCS and CaSki, under basal conditions. However, both contact and noncontact cocultures with human cervical fibroblasts resulted in the induction of APA expression in these SCC cells. APA expression was also induced in vivo when TCS cells were subcutaneously inoculated into nude mice. Furthermore, APA expression and enzymatic activity were enhanced by addition of the conditioned medium (CM) from fibroblast culture, but not by heat-treated CM. Among the various cytokines tested, vascular endothelial growth factor (VEGF) significantly increased APA activity, and induction of APA by the fibroblast CM was partly inhibited by anti-VEGF neutralizing antibody. Finally, APA cDNA-transfected APAoverexpressing TCS cells significantly reduced the Ang II-induced cell invasion ability as compared with parental or control vector-transfected TCS cells, although there was no significant difference in cellular proliferation among them. These results suggested the importance of tumor-stromal interaction for the regulation of APA expression in the microenvironment of cervical carcinoma and the potential role for this peptidase in regulating tumor invasion through inactivation of Ang II activity.

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Aminopeptidase A in human placenta

Cited by 56 publications

References 15 publications

Aminopeptidase A activity of the murine B-lymphocyte differentiation antigen BP-1/6C3.

Aminopeptidase A activity of the murine B-lymphocyte differentiation antigen BP-1/6C3.

Human Aminopeptidases: A Review of the Literature

Regulation of aminopeptidase A expression in cervical carcinoma: role of tumor–stromal interaction and vascular endothelial growth factor

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