Molecular Biology of Human Renin and Its Gene

Baxter, John D.; Duncan, Keith G.; Chu, William; James, Michael N.G.; Russell, Robert B.; Haidar, Mohammad A.; Denoto, Frances M.; Hsueh, Willa A.; Reudelhuber, Timothy L.

doi:10.1016/b978-0-12-571147-0.50011-1

Cited by 15 publications

(14 citation statements)

References 164 publications

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“…24 Moreover, a direct comparison of the levels of trypsin-activatable prorenin produced in transfected CHO cells with the levels of active renin secreted by AtT-20 cells (Figure 4) suggests that both enzymes may be affected by common structural features on prorenin. Although the effect of mutations on trypsin activation could affect our determinations of prorenin (which depend on trypsin cleavage), the net result would be an underestimation of the effect of mutations on the ability of AtT-20 cells to activate prorenin.…”

Section: Discussionmentioning

confidence: 99%

Molecular determinants of human prorenin processing.

et al. 1992

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In humans, active renin is generated by the removal of a 43-amino acid prosegment from the zymogen prorenin. This cleavage event is highly specific, occurring at only one of the seven pairs of basic amino acids in the body of preprorenin. This cleavage site selectivity is also displayed by a number of other proteases in vitro and in mouse pituitary AtT-20 cells transfected with a human preprorenin expression vector, suggesting that specificity of cleavage is directed in part by the primary sequence, the higher order structure, or both of prorenin itself. To test this hypothesis, single amino acid mutations were introduced in the region of human preprorenin surrounding the natural cleavage site, and the resultant recombinant proteins were expressed in cultured Chinese hamster ovary and AtT-20 cells. The results suggest that amino acids in addition to the pair of basic amino acids surrounding the cleavage site affect the ability of both trypsin and the endogenous AtT-20 processing enzyme to cleave prorenin. Notably, although a proline at position -4 is essential for processing of prorenin in AtT-20 cells and is correlated with predicted formation of a p-turn at this position, site-directed mutations suggest that this structural feature in addition to a pair of basic amino acids is not sufficient to lead to proteolytic activation of prorenin. Displacement of sequences surrounding the cleavage site to a position 10 amino acids toward the amino terminus led to partial processing of a mutated prorenin. Taken together, these results suggest that the ability of AtT-20 cells to cleave prorenin is directed primarily by specific amino acid recognition on the amino side of the sclssile bond and that additional determinants (perhaps structural) enhance the efficiency of the maturation step. (Hypertension 1992;20:782-787) KEY WORDS • enzyme precursors • renin • renin-angiotensin system R enin is an aspartyl protease and is the limiting component in the circulating renin-angiotensin system, an important modulator of blood pressure in mammals.

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Section: Discussionmentioning

confidence: 99%

Molecular determinants of human prorenin processing.

et al. 1992

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“…The renin-angiotensin system plays a key role in mammalian cardiovascular homeostasis through its control of sodium and fluid balance and its control of vascular tone (Baxter et al, 1989;Keeton and Campbell, 1980;Peach, 1977). These functions of the RAS have been better studied and understood in adult individuals.…”

Section: Introductionmentioning

confidence: 98%

Renin-angiotensin system genes in kidney development

Gomez

1997

Microsc. Res. Tech.

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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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Molecular Biology of Human Renin and Its Gene

Cited by 15 publications

References 164 publications

Molecular determinants of human prorenin processing.

Molecular determinants of human prorenin processing.

Renin-angiotensin system genes in kidney development

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

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