RRC ID 66112
Author Nakagawa T, Suzuki-Nakagawa C, Watanabe A, Asami E, Matsumoto M, Nakano M, Ebihara A, Uddin MN, Suzuki F.
Title Site-1 protease is required for the generation of soluble (pro)renin receptor.
Journal J Biochem
Abstract The extracellular domain of the (pro)renin receptor [(P)RR] is cleaved to generate the soluble form of (P)RR [s(P)RR]. Multiple clinical studies have revealed the association between serum/plasma s(P)RR levels and certain diseases, thereby suggesting a potential role for s(P)RR as a disease biomarker. Here, we investigated whether site-1 protease (S1P) is responsible for cleaving (P)RR to generate s(P)RR. Reduction of endogenous S1P with siRNA attenuated s(P)RR generation in Chinese hamster ovary (CHO) cells exogenously expressing human (P)RR with a C-terminal decahistidine tag [CHO/h(P)RR-10His cells]; conversely, overexpression of S1P by transient transfection increased s(P)RR generation. The S1P inhibitor PF429242 suppressed s(P)RR generation in CHO/h(P)RR-10His and human cervical carcinoma HeLa cells; however, the ADAM inhibitor GM6001 had no effect. The furin inhibitor Dec-RVKR-CMK had no effect on the amount of s(P)RR, but caused a slight increase in the size of the s(P)RR. Moreover, the reversible vesicle-trafficking inhibitor brefeldin A (BFA) enhanced the generation of large-sized s(P)RR; PF429242, but not Dec-RVKR-CMK, suppressed this BFA-induced s(P)RR formation. The size of s(P)RR generated during BFA treatment was reduced after removal of BFA; Dec-RVKR-CMK, but not PF429242, suppressed this conversion. Together, these results suggest that s(P)RR is generated by sequential processing by S1P and furin.
Volume 161(4)
Pages 369-379
Published 2017-4-1
DOI 10.1093/jb/mvw080
PII mvw080
PMID 28013223
MeSH Amino Acid Sequence Animals Brefeldin A / pharmacology CHO Cells Cricetinae Cricetulus Furin / metabolism HeLa Cells Humans Immunoblotting Models, Biological Proprotein Convertases / antagonists & inhibitors Proprotein Convertases / genetics Proprotein Convertases / metabolism* Protease Inhibitors / pharmacology RNA Interference Receptors, Cell Surface / genetics Receptors, Cell Surface / metabolism* Sequence Homology, Amino Acid Serine Endopeptidases / genetics Serine Endopeptidases / metabolism* Solubility
IF 2.23
Human and Animal Cells HeLa(RCB0007)