gms | German Medical Science

A human renin/ prorenin receptor (RER), which can specifically bind renin and prorenin, has recently been cloned. This receptor, which is highly expressed, in heart and brain, exerts a dual function: First, binding of renin to the RER increases renin's catalytic activity, and the receptor is able to unmask the catalytic activity of prorenin. Second, the RER induces a signal transduction cascade upon ligand binding involving activation of the MAP (mitogen-activated protein) kinases ERK1 and ERK2. Since little is known about the RER, we analyzed its function and signal transduction cascade. Initially, using RT/PCR and Northern blotting, we found evidence for an ubiquitous expression pattern of the human RER. Consistently, we were able to identify several transcriptional start sites by 5´-RACE and a high promoter activity using luciferase assays. In addition, by overexpressing tagged RER, we demonstrated an intracellular expression pattern in addition to the published cell-surface localization. RER activation by recombinant (but not extracted) renin in HeLa-S3 cells caused a strong ERK1/2 activation (+ 314% at 5 min). Interestingly, we could identify PLZF (promyelocytic zinc finger protein) as direct protein interaction partner of the RER by yeast two-hybrid screening. Our experiments indicate that the RER exhibits intracellular functions, and might - besides the activation of MAPK - transduce signals to the nucleus with PLZF as adaptor protein.