Purpose: This two-part review aims to consolidate information on renin
structure, synthesis, precursor processing, intracellular shunting an
d transcriptional control. Such revolutionary advances in the molecula
r knowledge of renin stem from the cloning of mouse renin complementar
y DNA in the early 1980s. Contents: Amongst many of the key studies su
ch as cloning of human, mouse and rat renin genes, which have been cru
cial to progress, several highlights covered in this part include: dif
ferences in DNA sequences that might explain species differences in ti
ssue-specific expression; identification of inactive renin as pro-reni
n, the activation site and the molecular explanation for this activati
on by many proteases; a different processing site for rat pro-renin; a
nd identification of cathepsin B as a likely pro-renin activator in ki
dney and a kallikrein as the activator of the duplicated mouse renin g
ene product. Conclusion: Cloning of the renin gene has greatly increas
ed our understanding of the processes that precede secretion of this i
mportant enzyme.