Intracellular retention of the extracellular domain of the (pro)renin receptor in mammalian cells.

As a component of the renin-angiotensin system, the (pro)renin receptor [(P)RR] activates prorenin along with intracellular signaling pathways. In this study, the glutathione S-transferase-fused extracellular domain of (P)RR expressed in mammalian cells was recovered in the detergent phase in detergent-based two-phase separation experiments, and intracellular localization was observed by immunocytochemistry, suggesting retention inside the cell through stable membrane association.

Structural insight into glucose dehydrogenase from the thermoacidophilic archaeon Thermoplasma volcanium.

Glucose dehydrogenase from the thermoacidophilic archaeon Thermoplasma volcanium (tvGlcDH) is highly active towards D-glucose and D-galactose, but does not utilize aldopentoses such as D-xylose as substrates. In the present study, the crystal structures of substrate/cofactor-free tvGlcDH and of a tvGlcDH T277F mutant in a binary complex with NADP and in a ternary complex with D-glucose and nicotinic acid adenine dinucleotide phosphate, an NADP analogue, were determined at resolutions of 2.6, 2.

[A case of Stage IV sigmoid colon cancer that achieved long-term survival with oral anticancer drugs].

An 80-year-old man presenting with abdominal distension was admitted to our hospital. He was diagnosed with sigmoid cancer with multiple liver and lung metastases. We first performed a sigmoidectomy to avoid obstruction, and then initiated chemotherapy with S-1(120mg/day).

[A case of complete response(CR)to S-1 and paclitaxel(PTX)combination therapy in a patient with unresectable gastric cancer].

We report a case of a patient with unresectable gastric cancer who showed complete response(CR)to S-1 and paclitaxel (PTX)combination therapy. The patient(a 67-year-old woman)was diagnosed with unresectable advanced gastric cancer with metastases in the Virchow's lymph nodes and para-aortic lymph nodes. Systemic chemotherapy with 70mg/m2 S-1 (days 1-14)and 70mg/m2 PTX(day 1)was administered every 3 weeks.

The coexistence of Ser84 in renin and His13 in angiotensinogen brings a pH profile of two separate peaks to the reaction of human renin and sheep angiotensinogen.

The pH dependence and kinetics parameters of renin-angiotensinogen reactions were determined using wild-type and S84G mutant human renins and wild-type and H13Y mutant sheep angiotensinogens. It is explained in this report that (i) renin catalyzes acidic and basic reactions of which the optimum pHs are 5.5 and 7.

Role of "handle" region of prorenin prosegment in the non-proteolytic activation of prorenin by binding to membrane anchored (pro)renin receptor.

A role of the "handle" region in the prorenin prosegment sequence was investigated to demonstrate the crucial non-proteolytic activation of prorenin by binding to the recombinant (pro)renin receptor on the COS-7 cell membrane. The plasmid DNA containing either rat or human (pro)renin receptor was transfected into the COS-7 cells. The highest amount of receptor was observed on the COS-7 cell membrane after 18 h transfection.

Ser84 of human renin contributes to the biphasic pH dependence of the renin-angiotensinogen reaction.

The pH dependence of the reaction of various renins was investigated using sheep angiotensinogen as a substrate. Human renin showed two separate peaks, but rat and mouse Ren1 renins showed one peak with a shoulder. A comparison of the predicted subsite residues of human renin with those of rat and mouse Ren1 renins revealed that Arg82, Ser84, Thr85, Ala229, and Thr312 are unique in the human sequence.

The His-Pro-Phe motif of angiotensinogen is a crucial determinant of the substrate specificity of renin.

The amino acid sequence His-Pro-Phe as N-terminal residues 6-8 of the natural renin substrate, angiotensinogen, is conserved among species. We investigated whether this His-Pro-Phe motif functions as the determinant of the substrate specificity of renin. Mutant angiotensinogens in which the Ile-His-Pro-Phe-His-Leu sequence at positions 5-10 of wild-type angiotensinogen was replaced by either His-Pro-Phe-His-Leu-Leu or Ala-Ile-His-Pro-Phe-His were cleaved by renin at the C-terminal side of residues 9 and 11, respectively, while wild-type angiotensinogen was cleaved at residue 10.

Efficient production of recombinant human (pro)renin utilizing a decahistidine tag attached at the C-terminus.

Human prorenin attached by a decahistidine tag at the C-terminus was produced in Chinese hamster ovary cells. The tagged protein secreted into the culture medium was in the inactive prorenin form, and was activated to mature renin by proteolytic removal of its prosegment by trypsin in the same manner as native prorenin. The tagged (pro)renin was efficiently purified by metal-chelate affinity chromatography.