Expression and Enzymatic Activity of Human Disintegrin and Metalloproteinase ADAM19/Meltrin Beta

Wei, Ping; Zhao, Yunge; Li, Zhuang; Ruben, Steve; Sang, Qing‐Xiang Amy

doi:10.1006/bbrc.2000.4200

Cited by 57 publications

(71 citation statements)

References 30 publications

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“…Based on the sequence homology of the zinc-binding site to other metalloproteinases, it has been determined that ADAM19 is an active metalloproteinase with enzyme activity. Indeed, ADAM19 does cleave human alpha2-macroglobulin, generating products of 98 kDa and 76 kDa (9). In CAN, ADAM19 may have yet undefined functions related to protein degradation and renal tissue remodeling.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of ADAM19 in Chronic Allograft Nephropathy

Melenhorst¹,

Heuvel²,

Stegeman

et al. 2006

American Journal of Transplantation

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ADAM19 (a disintegrin and metalloproteinase 19) isinvolved in cell-cell and cell-matrix interactions and tumor necrosis factor (TNF)-alpha shedding. We studied ADAM19 in chronic allograft nephropathy (CAN) nephrectomies and in normal human kidneys. Reverse transcriptase (RT) PCR revealed an upregulation of ADAM19 mRNA in CAN when compared with control kidneys (p = 0.002). Using RNA in situ hybridization (ISH), we detected moderate ADAM19 mRNA expression in vascular smooth muscle cells (SMCs) and distal tubuli of control kidneys. In CAN, massive ADAM19 expression was detected in SMCs, distal tubuli, glomerular sclerotic lesions and inflammatory CD4 + cells. To determine whether ADAM19 is specifically related to CAN, we studied transplant biopsies with and without CAN, acute rejection and non-transplant-related kidney diseases: interstitial fibrosis (IF), interstitial atrophy, glomerular fibrosis and interstitial inflammation. In various renal structures, ADAM19 mRNA was significantly higher in CAN when compared with renal allografts without CAN or acute rejection. ADAM19 expression in renal endothelium was significantly higher in acute rejection when compared with renal allografts without CAN. When compared to CAN, ADAM19 was expressed to a similar extent in non-transplant-related interstitial and glomerular fibrosis, interstitial atrophy and inflammation. Although these observational data do not establish a cause and effect relationship, ADAM19 may have a modulatory role in the dysfunctional renal allograft state.

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Section: Discussionmentioning

confidence: 99%

Upregulation of ADAM19 in Chronic Allograft Nephropathy

Melenhorst¹,

Heuvel²,

Stegeman

et al. 2006

American Journal of Transplantation

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“…These doublets may be differentially glycosylated forms. According to protein sequence analyses, hADAM19 has five potential glycosylation sites (27). Indeed, endoglycosidase F converted the doublets into a single pro-or active form, respectively (data not shown).…”

Section: Removal Of the Hadam19 Prodomain Is Dependent On Furinmentioning

confidence: 94%

“…␣ 2 -M Trapping Assay to Determine Endopeptidase Activity of hADAM19 Species-The detailed experimental procedure was previously reported (27,28). Briefly, 10 l of the fraction containing purified soluble hADAM19 was mixed with 24 l of ␣ 2 -M (0.2 unit/ml), adjusted to a total volume of 100 l by adding HEPES buffer (50 mM HEPES, pH 7.5, 200 mM NaCl, 10 mM CaCl 2 , 25 M ZnCl 2 , 0.05% Brij-35), and incubated at 37°C for 1-5 days.…”

Section: Methodsmentioning

confidence: 99%

Intracellular Activation of Human Adamalysin 19/Disintegrin and Metalloproteinase 19 by Furin Occurs via One of the Two Consecutive Recognition Sites

Kang¹,

Zhao²,

Pei³

et al. 2002

Journal of Biological Chemistry

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RR to AA mutant, which abolished both furin recognition sites. Moreover, the zymogens were not converted into their active forms in two furindeficient mammalian cell lines; co-expression of hADAM19 and furin in these two cell lines restored zymogen activation. Finally, co-localization between furin and hADAM19 was identified in the endoplasmic reticulumGolgi complex and/or the trans-Golgi network. This report is the first thorough investigation of the intracellular activation of adamalysin 19, demonstrating that furin activated pro-hADAM19 in the secretory pathway via one of the two consecutive furin recognition sites.The adamalysin, ADAM 1 (for a disintegrin and metalloprotease), or metalloprotease/disintegrin/cysteine-rich family includes proteins containing disintegrin-and metalloproteaselike domains. These proteinases are involved in diverse processes, such as development, cell-cell interaction, and protein ectodomain shedding (1-5). For example, ADAM10/kuzbanian (KUZ) and ADAM17/tumor necrosis factor-␣ convertase play key roles in the processing of both Notch1 receptor, which is critical in development, and amyloid precursor protein, which is related to the pathogenesis of Alzheimer's disease (3,4,6). Six different ADAMs, ADAM2, -9, -12, -15, -23, and -28, are able to interact with integrins such as ␣

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“…In the ADAM family, ADAM19 is localized in the Golgi. 18,19 Dual transfection with (P)RR-Venus and ADAM19-V5 significantly increased the ratio of the CTF-(P)RR and the dominant negative ADAM19 reversed this CTF-(P)RR increase. Yokozeki et al reported that the shedding of Neuregulin b1 is mediated by ADAM19 in the Golgi.…”

Section: Adam19 Cleaves (P)rrmentioning

confidence: 95%

The (pro)renin receptor is cleaved by ADAM19 in the Golgi leading to its secretion into extracellular space

Yoshikawa

Aizaki

Kusano³

et al. 2011

Hypertens Res

113

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The (pro)renin receptor ((P)RR), which is a recently discovered molecule of the renin-angiotensin system, plays an important role in the development of cardiovascular diseases. However, the molecular properties and the subcellular distribution of (P)RR remain controversial. In this study, (P)RR-Venus in Chinese hamster ovary (CHO) cells ((P)RR-Venus-CHO) or endogenous (P)RR in human vascular smooth muscle cells (VSMC) were constitutively cleaved without any stimulation, and secretion of the aminoterminal fragment (NTF-(P)RR) into the media was determined using western blot analysis. Immunofluorescent analysis showed robust expression of (P)RR in the endoplasmic reticulum (ER) or the Golgi but not in the plasma membrane. Moreover, we identified ADAM19, which is expressed in the Golgi, as one of cleaving proteases of (P)RR. Transfected ADAM19 evoked the shedding of (P)RR, whereas transfected dominant negative ADAM19 suppressed it. Although (P)RR contains a furin cleavage site, neither the furin-deficient LoVo cells nor furin inhibitor-treated VSMC lost NTF-(P)RR in the media. The secreted NTF-(P)RR induced the renin activity of prorenin in the extracellular space. We describe that (P)RR is mainly localized in the subcellular organelles, such as the ER and Golgi, and (P)RR is cleaved by ADAM19 in the Golgi resulting in two fragments, NTF-(P)RR and CTF-(P)RR. These results may suggest that (P)RR is predominantly secreted into the extracellular space. Hypertension Research (2011) 34, 599-605; doi:10.1038/hr.2010.284; published online 27 January 2011Keywords: ADAM19; ectodomain shedding; (pro)renin receptor; renin-angiotensin system INTRODUCTION The (pro)renin receptor ((P)RR) is a recently discovered molecule of the renin-angiotensin system (RAS), which plays pivotal roles in the regulation of the cardiovascular system under normal and pathological conditions. (P)RR binds both renin and prorenin, which is the precursor form of renin. 1 Although the binding of renin to (P)RR may increase its catalytic activity, the binding affinity between (P)RR and renin is lower than that of (P)RR and prorenin. These results indicate that it may be necessary to focus on the interaction between (P)RR and prorenin. Prorenin does not display protease activity in the plasma because the enzymatic cleft is covered by the prosegment. 2 However, the binding of prorenin to (P)RR evokes the renin activity without removal of its prosegment. This nonproteolytic activation of prorenin contributes to the activation of the local RAS. In addition to the enzymatic activity, renin/prorenin has been shown to provide other (P)RR-mediated effects. 3 The binding of renin/prorenin to (P)RR induces the activation of intracellular signaling, including the p38 MAP kinase-HSP27 cascade, the PI3K pathway and the ERK 1/2 pathway; these effects occur independently of angiotensin II, which is a final product of RAS. 2,4,5 Although this evidence strongly supports (P)RR localization in the plasma membrane, the subcellular localization of (P)RR remains unknown. (P)R...

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Expression and Enzymatic Activity of Human Disintegrin and Metalloproteinase ADAM19/Meltrin Beta

Cited by 57 publications

References 30 publications

Upregulation of ADAM19 in Chronic Allograft Nephropathy

Upregulation of ADAM19 in Chronic Allograft Nephropathy

Intracellular Activation of Human Adamalysin 19/Disintegrin and Metalloproteinase 19 by Furin Occurs via One of the Two Consecutive Recognition Sites

The (pro)renin receptor is cleaved by ADAM19 in the Golgi leading to its secretion into extracellular space

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