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• W2110200349 abstract "Prorenin binding to the prorenin receptor [(P)RR] results in nonproteolytic activation of prorenin but also directly (i.e., independent of angiotensin generation) activates signal transduction cascades that can lead to the upregulation of profibrotic factors. The (P)RR is an accessory protein of vacuolar-type H⁺-ATPase (V-ATPase) and is required for V-ATPase integrity. In addition, in collecting duct cells, prorenin-induced activation of Erk depends on V-ATPase activity. However, whether prorenin binding to the (P)RR directly regulates V-ATPase activity is as yet unknown. Here, we studied the effect of prorenin on plasma membrane V-ATPase activity in Madin-Darby canine kidney clone 11 (MDCK.C11) cells, which resemble intercalated cells of the collecting duct. Prorenin increased V-ATPase activity at low nanomolar concentrations, and the V-ATPase inhibitor bafilomycin A1, but not the angiotensin II type 1 and 2 receptor blockers irbesartan and PD-123319, prevented this. Increased, but not basal, V-ATPase activity was abolished by small interfering RNA depletion of the (P)RR. Unexpectedly, the putative peptidic (P)RR blocker handle region peptide also increased V-ATPase activity in a (P)RR-dependent manner. Finally, [Arg⁸]-vasopressin-stimulated V-ATPase activity and cAMP production were also abolished by (P)RR depletion. Our results show that in MDCK.C11 cells, the (P)RR is required for prorenin-dependent and -independent regulation of V-ATPase activity." @default.
• W2110200349 created "2016-06-24" @default.
• W2110200349 creator A5013469844 @default.
• W2110200349 creator A5021707048 @default.
• W2110200349 creator A5059858622 @default.
• W2110200349 creator A5065678814 @default.
• W2110200349 creator A5070077025 @default.
• W2110200349 date "2013-08-01" @default.
• W2110200349 modified "2023-10-13" @default.
• W2110200349 title "(Pro)renin receptor is required for prorenin-dependent and -independent regulation of vacuolar H⁺-ATPase activity in MDCK.C11 collecting duct cells" @default.
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• W2110200349 doi "https://doi.org/10.1152/ajprenal.00037.2013" @default.
• W2110200349 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23698123" @default.
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