The biosynthetic pathway of renin in mouse submandibular gland.
The present study set out to demonstrate the biosynthesis of a prorenin and its processing in the cell, using the richest known natural source of renin, the mouse submandibular gland. Cell-free translation of total poly(A+) RNA or mRNA selected using a renin cDNA yielded Mr = 45,000 preprorenin which in the presence of dog pancreatic microsomal membranes, was converted to Mr = 43,000 prorenin. The latter was seen during in vitro labeling of tissue with [35S]methionine. Prorenin was synthesized first and converted rapidly to Mr = 38,000 single chain renin. Renin was then hydrolyzed slowly to give two chains of Mr = 33,000 and 5,000 held together by disulfide bonds. The Mr = 38,000 and 33,000 species had similar peptide maps. Western blotting of fractions from a pepstatin affinity column identified the separation of prorenin from renin. The results suggested that both single and two-chain renin have an exposed active site. Testosterone stimulated synthesis of prorenin during in vitro labeling of female tissue. Thus, mouse renin is synthesized as a preprorenin (Mr = 45,000) which is converted to a prorenin (Mr = 43,000) and then to renin (Mr = 38,000) by rapid processing within the cell, after which renin is cut slowly to give a two-chain form.
D000818:Animals; D004285:Dogs; D004792:Enzyme Precursors / Q000235:genetics*; D007425:Intracellular Membranes / Q000201:enzymology; D007700:Kinetics; D051379:Mice; D008861:Microsomes / Q000201:enzymology; D008970:Molecular Weight; D010179:Pancreas / Q000201:enzymology; D010446:Peptide Fragments / Q000032:analysis; D011061:Poly A / Q000235:genetics; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012083:Renin / Q000235:genetics*; D013363:Submandibular Gland / Q000201:enzymology*
D004792:Enzyme Precursors; D010446:Peptide Fragments; D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D012083:Renin