Insulin secretory granule biogenesis and the proinsulin-processing endopeptidases.
The insulin storage granule of the pancreatic beta cell is assembled within the trans Golgi network from around 50 or so gene products many of which are synthesized coordinately with the major component, proinsulin. An important contribution to our understanding of the regulation of this process has come from studies of the post-translational processing of proinsulin and of other proteins which are stored in the granule, particularly the processing enzymes themselves. The present review focusses on recent insights into the molecular nature of the processing machinery, and the granule Ca(2+)-dependent subtilisin-related endopeptidases which catalyse the initial rate-limiting step in the enzymic conversion of proinsulin.
Hutton
J C
JC
Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, UK.
D000595:Amino Acid Sequence; D000818:Animals; D001315:Australia; D001363:Awards and Prizes; D003594:Cytoplasmic Granules / Q000502:physiology* / Q000648:ultrastructure; D003920:Diabetes Mellitus / Q000266:history; D010450:Endopeptidases / Q000378:metabolism*; D005060:Europe; D049673:History, 20th Century; D006801:Humans; D007328:Insulin / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000502:physiology* / Q000648:ultrastructure; D011384:Proinsulin / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012955:Societies, Medical; D013379:Substrate Specificity; D006113:United Kingdom
D007328:Insulin; D011384:Proinsulin; D010450:Endopeptidases; C054196:proinsulin endopeptidase I; C061496:proinsulin endopeptidase II