Purification of renin and prorenin.

Inagami, Tadashi

doi:10.1161/01.hyp.18.3.241

Cited by 15 publications

(9 citation statements)

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“…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)RR is found on the cell surface of adipose stromal cells and in mesangial cells that overexpress (P)RR, whereas (P)RR is expressed in the intracellular compartments in vascular smooth muscle cells (VSMC) and is overexpressed in HeLa-S3 cells.…”

Section: Introductionmentioning

confidence: 70%

“…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.…”

Section: Introductionmentioning

confidence: 99%

“…(P)RR is found on the cell surface of adipose stromal cells and in mesangial cells that overexpress (P)RR, whereas (P)RR is expressed in the intracellular compartments in vascular smooth muscle cells (VSMC) and is overexpressed in HeLa-S3 cells. 2,5,6,7 Furthermore, Batenburg et al demonstrated that (P)RR is recycled between the cell surface and the intracellular compartment in VSMC that were harvested from human (P)RR transgenic rats. 8 Recently, Cousin et al reported that there are soluble and receptor forms of (P)RR; in addition, a 8.9 kDa protein, M8-9, which corresponds to the carboxyl-terminal amino acid sequences of (P)RR, associates with the vacuolar H + -ATPase in the chromaffin cells of the adrenal medulla.…”

Section: Introductionmentioning

confidence: 99%

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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

119

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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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Section: Introductionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

119

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“…9,10 The precursor of renin is inactive, because the prosegment region with 43 amino acid residues covers the active site of renin with 339-341 residues. [11][12][13][14][15] Activation of prorenin can take place either proteolytically or non-proteolytically. Proteolytic activation has been observed in vitro by treatments of some proteases, [16][17][18][19][20][21] thereby, irreversibly removing the prosegment.…”

Section: Introductionmentioning

confidence: 99%

Biochemical properties of renin and prorenin binding to the (pro)renin receptor

Nabi

Suzuki

2009

Hypertens Res

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The discovery of (pro)renin receptor, (P)RR, has made the renin-angiotensin system (RAS) more multifaceted. Interaction of renin and prorenin with this receptor has set a new perspective about the physiological functions, activation mechanism and pathophysiological roles of renin/prorenin. Uses of peptides mimicking the structure of the ligands have been very effective for determining structure-function relationship between the ligands and receptor. The probable pivotal role of decoy peptide region (R 10P IFLKRMPSI 19P ) of prorenin prosegment was suggested for higher binding affinity of prorenin to (P)RR than that of mature renin. Recently, 'hinge' region peptide (S 149 QGVLKEDVF 158 ) in renin/prorenin molecule has been reported. Both renin and prorenin can interact with (P)RR through the 'hinge' region. Furthermore, it has been proposed that prorenin has multiple binding sites whereas renin has a single binding site for (P)RR. To comprehend the activation mechanism of renin and prorenin after receptor binding, it is very important to understand their interaction with the receptor. Several kinds of peptides designed from the regions of the tertiary structure of renin and predicted model of prorenin facilitated the study of the in vitro binding mechanisms for renin and prorenin to (P)RR. Here, a series of recent in vitro studies was reviewed to discuss a possible binding mechanism of renin/prorenin to the (P)RR.

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“…Prorenin has a prosegment with 43 amino acid residues attached to the N terminus of mature renin with 339-341 residues. [1][2][3] The prosegment has been considered to associate with mature renin to prevent interaction with angiotensinogen, its macromolecular renin substrate. [4][5][6] Prorenin does not proteolytically self-activate like pepsinogen, and its blood circulating level is ten times higher than that of mature renin.…”

Section: Introductionmentioning

confidence: 99%

Nonproteolytic activation of prorenin by the (pro)renin receptor is blocked by decoy peptide

Suzuki

2007

J Renin Angiotensin Aldosterone Syst

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Purification of renin and prorenin.

Cited by 15 publications

References 146 publications

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

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

Biochemical properties of renin and prorenin binding to the (pro)renin receptor

Nonproteolytic activation of prorenin by the (pro)renin receptor is blocked by decoy peptide

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