Proprotein-processing endopeptidases of the insulin secretory granule.
Enzymological studies have implicated two Ca2+ dependent endopeptidases in the conversion of proinsulin to insulin: a type 1 activity and a type 2 activity which cleave on the C-terminal side of R31R32 and K64R65 in proinsulin, respectively. These activities were further characterized and their relationship to the mammalian family of subtilisin-like proteases was investigated. PC2 was expressed in neuroendocrine tissues and in insulinoma secretory granule fractions predominantly as a 65kDa protein. On anion-exchange chromatography of solubilized granules, PC1/3 immunoreactivity comigrated with a peak of type 1 activity whereas PC2 immunoreactivity coeluted with the peak of type 2 endopeptidase activity. PC2 antiserum gave a specific immunoprecipitation of type 2 activity from insulin granule extracts. It was concluded that the PC2 gene-product has type 2 endopeptidase activity.
Bailyes
E M
EM
Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, UK.
Bennett
D L
DL
Hutton
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D003594:Cytoplasmic Granules / Q000378:metabolism*; D007328:Insulin / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D011384:Proinsulin / Q000378:metabolism*; D045706:Proprotein Convertase 2; D011499:Protein Processing, Post-Translational; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism
D007328:Insulin; D011384:Proinsulin; D012697:Serine Endopeptidases; D045706:Proprotein Convertase 2