(Pro)Insulin processing: a historical perspective.
Insulin, the major secreted product of the beta-cells of the islets of Langerhans, is initially synthesized as a precursor (preproinsulin), from which the mature hormone is excised by a series of proteolytic cleavages. This review provides a personal narrative of some of the key research projects leading to the identification of the central processing enzymes as proprotein convertase 1, proprotein convertase 2, and carboxypeptidase E. It also discusses the central roles of the intragranular environment and chaperone-like proteins in modulating processing activity.
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, CO, USA. Howard.Davidson@UCHSC.edu
Howard W
HW
Davidson
D000595:Amino Acid Sequence; D000818:Animals; D043423:Carboxypeptidase H / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D011384:Proinsulin / Q000378:metabolism*; D045664:Proprotein Convertase 1 / Q000378:metabolism*; D045706:Proprotein Convertase 2 / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D014357:Trypsin / Q000737:chemistry
D007328:Insulin; D018832:Molecular Chaperones; D011384:Proinsulin; D043423:Carboxypeptidase H; D014357:Trypsin; D045664:Proprotein Convertase 1; D045706:Proprotein Convertase 2