Prorenin-induced intracellular signaling pathway is not fully elucidated. We investigated whether the (pro)renin receptor mediates epidermal growth factor (EGF) receptor transactivation through angiotensin (Ang) II-dependent and -independent pathways in human embryo kidney 293 cells. Prorenin (2 nmol/L) caused biphasic phosphorylation of EGF receptor (Tyr992) and extracellular signal-regulated ...

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 mem...

The renin-angiotensin-aldosterone system regulates homeostasis of salt and water, vasoconstriction, and remodeling in cardiovascular and renal cells via activation of intracellular signaling pathway. Prorenin, the precursor of renin, had long been considered to be an inactive form. However, a receptor--the (pro)renin receptor--that binds to both renin and prorenin has been recently identified. ...

Although elevated plasma prorenin levels are commonly found in diabetic patients and correlate with microvascular complications, the pathological role of these increases, if any, remains unclear. Prorenin/renin binding to the prorenin/renin receptor [(p)RR] enhances the efficiency of angiotensinogen cleavage by renin and unmasks prorenin catalytic activity. We asked whether plasma prorenin coul...

The rat recombinant renin/prorenin receptor (AB188298 in DDJB), which conjugated with FLAG epitope in its N-terminus, was expressed in a baculovirus expression system. The recombinant receptor, prepared from the cytoplasmic fraction of the insect cells, was identified by Western blotting using anti-FLAG antibody. Prorenin as well as renin bound to the receptor with different binding affinities....

The (pro)renin receptor is a single-spanning membrane protein that binds both renin and its inactive precursor prorenin. The receptor binding enhances the catalytic activity of renin and induces non-proteolytic activation of prorenin as well as triggers intracellular signaling with either renin or prorenin as a ligand. Three-dimensional structural information of (pro)renin receptor is important...

Prorenin, the precursor of renin, exists in circulating blood at concentrations that are 5 to 10 higher than those of renin. For many years, prorenin was considered to be an inactive form of renin with no physiological role. Then, in the mid-80s of the last century, Luetscher et al reported that the levels of circulating prorenin (but not renin) are increased in diabetic subjects.1 Subsequent s...

Recently we showed that fructose feeding in rats induced nonproteolytic activation of prorenin and subsequent angiotensin II production in skeletal muscle. In addition, a pharmacological inhibitor of prorenin/(pro)renin receptor interaction attenuated the development of insulin resistance. However, the inhibitor did not ameliorate the glucose intolerance in transgenic rats overexpressing the hu...

PURPOSE Recently, it was revealed that the inhibition of nonproteolytic activation of prorenin led to significant suppression of ocular inflammation in endotoxin-induced uveitis. The purpose of the present study was to investigate whether nonproteolytically activated prorenin plays a role in ischemia-induced retinal neovascularization. METHODS C57BL/6 neonatal mice were reared in an 80% conce...

Many lines of evidence implicate the reninangiotensin system in the pathogenesis of diabetic retinopathy. A recent multicenter trial showed that angiotensin II type 1 (AT1) receptor blockade (ARB) reduced the incidence of retinopathy in type 1 diabetic patients and improved the regression of retinal disease in type 2 diabetic patients (1,2). However, the failure of ARB to prevent progression of...