The role of prohormone convertases in insulin biosynthesis : Evidence for inherited defects in their action in man and experimental animals

Diabetes and Metabolism

Volumn 22, Issue 2, 1996, Pages 94-104

  Steiner, D F ^a,b   Rouille Y ^b,c   Gong, Q ^b,d   Martin, S ^b   Carroll, R ^b   Chan, S J ^b  

^a HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^b UNIVERSITY OF CHICAGO   (United States)

^c UNIVERSITY OF GENEVA MEDICAL SCHOOL   (Switzerland)

^d UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

Author keywords

Biosynthesis; Carboxypeptidase; Proglucagon; Proinsulin; Subtilisin like protein convertases

Indexed keywords

CARBOXYPEPTIDASE H; DIPEPTIDYL CARBOXYPEPTIDASE; HORMONE PRECURSOR; PREPROINSULIN; PROGLUCAGON; PROINSULIN;

CONFERENCE PAPER; HUMAN; INSULIN SYNTHESIS;

ANIMALS; ASPARTIC ENDOPEPTIDASES; C-PEPTIDE; DIABETES MELLITUS, TYPE 1; DIABETES MELLITUS, TYPE 2; GLUCAGON; HUMANS; INSULIN; ISLETS OF LANGERHANS; OBESITY; ORGAN SPECIFICITY; PROINSULIN; PROPROTEIN CONVERTASE 2; PROPROTEIN CONVERTASES; SUBTILISINS;

EID: 0029988849     PISSN: 12623636     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (72)

1. Bliss M. The Discovery of Insulin. Chicago, The University of Chicago Press, 1982
2. Sanger F Chemistry of insulin. Science, 1959, 129, 1340-1344.
3. Sanger F. Nicklen S, Coulson AR. DNA sequencing with chainterminating inhibitors. Proc Natl Acad Sci USA, 1977, 74, 5463-5467.
4. Schäfer EA. An introduction to the study of internal secretion. In : The Endocrine Organs. Longmans, Green, and Co., 1916, 128.
5. Scott VB On the existence of pro-secretin. Am J Physiol. 1935, 112, 511-518.
6. Steiner DF, Oyer PE. The biosynthesis of insulin and a probable precursor of insulin by a human islet cell adenoma. Proc Natl Acad Sci USA, 1967, 57, 473-480.
7. Steiner DF, Smeekens SP, Ohagi S, Chan SJ. The new enzymology of precursor processing endoproteases. J Biol Chem, 1992, 267, 23435-23438.
8. Julius D, Brake A. Blair L. Kunisawa R, Thorner J. Isolation of the putative structural gene for the lysine-arginine-cleaving endopeptidase required for processing of yeast prepro-a-factor. Cell, 1984, 37, 1075-1089.
9. Fuller RS, Sterne RE, Thorner J. Enzymes required for yeast prohormone processing. Ann Rev Physiol, 1988, 50, 345-362.
10. Fuller RS, Brake AJ. Thonier J. Intracellular targeting and structural conservation of a prohormone-processing endoprotease. Science, 1989, 246, 482-486.
11. Mizuno K. Nakamura T. Ohshima T, Tanaka S, Matsuo H. Yeast Kex2 gene encodes an endopeptidase homologous to subtilisin-like serine proteases. Biochem Biophys Res Commun, 1988, 156, 246-254.
12. Smeekens SP, Steiner DF. Identification of a human insulinoma cDNA encoding a novel mammalian protein structurally related to the yeast dibasic processing protease Kex2. J Biol Chem, 1990, 205, 2997-3000.
13. Seidah NG, Marcinkiewicz M. Benjannet S, Gaspar L, Beaubien G, Mattei MG et atlCloning and primary sequence of a mouse candidate prohormone convertase PC1 homologous to PC2, furin and Kex2 : Distinct chromosomal localization and messenger RNA distribution in brain and pituitary compared to PC2 Molec Endo, 1991, 5, 111-122.
14. Smeekens SP, Avruch AS, LaMendola J. Chan SJ, Steiner DF Identification of a cDNA encoding a second putative prohormone convertase related to PC2 in AtT20 cells and islets of Langerhans. Proc Natl Acad Sci USA, 1991, 88, 340-344.
15. Roebroek AJM, Schalken JA, Leunissen JAM, Onnekink C, Bloemers HPJ, Van de Ven WJM. Evolutionary conserved close linkage of the c-fes/fps proto-oncogene and genetic sequences encoding a receptor-like protein. EMBO J, 1986, 5, 2197-2202
16. Van de Van WJM. Voorberg J, Fontijan R et al. Furin is a subtilisin-like proprotein processing enzyme in higher eukaryotes. Molec Biol Reports, 1990, 14, 265-275.
17. Wise RJ, Bavr PJ, Wong PA, Kiefer MC. Brake AJ, Kaufman RJ. Expression of a human proprotein processing enzyme : Correct cleavage of the von Willebrand factor precursor at a paired basic amino acid site. Proc Natl Acad Sci USA, 1990, 87, 9378-9382.
18. Kiefer MC, Tucker JE, Joh R, Landsberg KE, Saltman D, Barr PJ. Identification of a second human subtilisin-like protease gene in the fes/fps region of chromosome 15. DNA Cell Biol, 1991, 10, 757-769.
19. Nakayama K, Kim W-S, Torij S et al. Identification of the fourth member of the mammalian endoprotease family homologous to the yeast Kex2 protease. J Biol Chem, 1992, 207, 5897-5900.
20. Nakagawa T, Hosaka M, Torii S, Watanabe T. Murakami K, Nakayama K. Identification and functional expression of a new member of the mammalian Kex2-like processing endoprotease family : Its striking structural similarity to PACE4. J Biochem. 1993, 113, 132-135.
21. Lusson J. Vieau D, Hamelin J. Day R, Chrétien M. Seidah NG. cDNA structure of the mouse and rat subtilisin/kexin-like PC5 : A candidate proprotein convertase expressed in endocrine and nonendocrine cells. Proc Natl Acad Sci USA, 1993, 90, 6691-6695.
22. Scopsi L, Gullo M, Rilke F, Martin R, Steiner DF. Proprotein convertases (PC1/PC3 and PC2) in normal and neoplastic human tissues : Their use as markers of neuroendocrine differentiation. J Clin Endocrinol Metab. 1995, 80, 294-301.
23. Chan SJ, Oliva AA Jr, LaMendola J. Grens A. Bode H, Steiner DF. Conservation of the prohomone convertase gene family in metazoa : Analysis of cDNAs encoding a PC3-like protein from hydra. Proc Natl Acad Sci USA, 1992, 89, 6678-6682.
24. Molloy SS, Thomas L, Van Slyke JK, Stenberg PE, Thomas G. Intracellular traffkicking and activation of the furin proprotein convertase : localization to the TGN and recycling from the cell surface. EMBO J. 1994, 13, 18-33.
25. Vey M. Schafer W. Berghöfer S, Klenk H-D, Garten W. Maturation of the trans-Golgi network protease furin : compartmentalization of propeptide removel substrate cleavage, and COOH-terminal truncation. J Cell Biol. 1994, 127, 1829-1842.
26. Molloy SS, Bresnahan PA, Leppla SH, Klimpel KR, Thomas G. Human furin is a calcium-dependent serine endoprotease that recognizes the sequences Arg-X-X-Arg and efficiently cleaves anthrax toxin protective antigen. J Biol Chem, 1992, 267, 16396-16402.
27. Rehemtulla A, Barr PJ, Rhodes CJ, Kaufman RJ PACE4 is a member of the mammalian propeptidase family that has overlapping but not identical substrate specificity to PACE Biochemistry, 1993, 32, 11586-11590.
28. Shennan KIJ, Taylor NA, Jermany JL, Matthews G, Docherty K Differences in pH optima and calcium requirements for maturation of the prohormone convertases PC2 and PC3 indicates different intracellular locations for these events J Biol Chem, 1995, 270, 1402-1407.
29. Lindberg I, van den Hurk WH, Bui C, Batie CJ. Enzymatic characterization of immunopurified prohormone convertase 2 : potent inhibition by a 7B2 peptide fragment. Biochemistry, 1995, 34, 5486-5493.
30. Vindrola O, Lindberg I Biosynthesis of the prohormone convertase mPC1 in AtT-20 cells. Mole Endo, 1992, 6, 1088-1094.
31. Zhou Y, Lindberg I. Enzymatic properties of carboxyl-terminally truncated prohormone convertase 1 (PC1/SPC3) and evidence of autocatalytic conversion. J Biol Chem, 1995, 269, 18408-18413
32. Orci L. Ravazzola M, Amherdt M, Madsen O, Vassalli J-D. Perrelet A. Direct identification of prohormone conversion site in insulin-secreting cells. Cell. 1995, 42, 671-682
33. Tooze J, Hollinshead M, Frank R, Burke B. An antibody specific for an endoproteolytic cleavage site provides evidence that proopiomelanocortin is packaged into secretory granules in AtT20 cells before its cleavage. J Cell Biol, 1987, 105, 155-162.
34. Guest PC, Arden SD, Bennett DL, Clark A, Rutherford NG, Hutton JC. The post-translational processing and intracellular sorting of PC2 in the islets of Langerhans. J Biol Chem, 1992, 267, 22401-22406
35. Shennan KIJ, Seal AJ, Smeekens SP, Steiner DE Docherty K. Site-directed mutagenesis and expression of PC2 in microinjected Xenopus Oocytes J Biol Chem, 1991, 266, 24011-24017.
36. Benjannet S, Rondeau N, Paquet L et al Comparative biosynthesis, covalent post-translational modifications and efficiency of prosegment cleavage of the prohormone convertases PC1 and PC2 : glycosylation, sulphation and identification of the intracellular site of prosegment cleavage of PC1 and PC2. Biochem J, 1993, 294, 735-743.
37. Lipkind G, Gong Q, Steiner DF. Molecular modelling of the substrate specificity of prohormone convertases PC2 and PC1/PC3. J Biol Chem, 1995, 22, 13277-13284.
38. Braks JAM. Martens GJM 7B2 is a neuroendocrine chaperone that transiently interacts with prohormone convertase PC2 in the secretory pathway. Cell, 1994, 78, 263-273.
39. Zhu X, Lindberg I 7B2 facilitates the maturation of proPC2 in neuroendocrine cells and is required for the expression of enzymatic activity. J Cell Biol, 1995, in press.
40. Zhou A, Bloomquist BT, Mains RE The prohormone convertases PC1 and PC2 mediate distinct endoproteolytic cleavages in a strict temporal order during proopiomelanocortin biosynthetic processing. J Biol Chem. 1993, 268, 1763-1769.
41. Day R, Schafer MK-H. Watson SJ, Chrétien M. Seidah NG Distribution and regulation of the prohormone convertases PC1 and PC2 in the rat pituitary. Molec Endo, 1992, 6, 485-497.
42. Thomas L, Leduc NDOR, Thorne BA, Smeekens SP, Steiner DF, Thomas G. Kex2-likc endoproteases PC2 and PC3 accurately cleave a model prohormone in mammalian cells Evidence for a common core of neuroendocrine processing enzymes. Proc Natl Acad Sci USA, 1991, 88, 5297-5301
43. Benjannet S, Rondeau N, Day R, Chrétien M, Seidah NG, PC1 and PC2 are proprotein convertases capable of cleaving proopiomelanocortin at distinct pairs of basic residues. Proc Natl Acad Sci USA, 1991, 88, 3564-3568.
44. Smeekens SP, Montag Ag, Thomas G et al. Proinsulin processing by the subtilisin-related proprotein convertases furin, PC2 and PC3, Proc Natl Acad Sci USA, 1992, 89, 8822-8826.
45. Bailyes EM, Shennan KIJ, Seal AJ et al. A member of the eukaryotic subtilisin family (PC3) has the enzymic properties of the Type 1 proinsulin-converting endopeptidase. Biochem J, 1992, 285, 391-394.
46. Bennett DL, Bailyes EM, Nielsen G et al. Identification of the Type 2 proinsulin processing endopeptidase as PC2, a member of the eukaryote subtilisin family. J Biol Chem, 1992, 267, 15229-15236.
47. Rhodes CJ, Lincoln B, Shoelson SE. Preferential cleavage of des-31,32-proinsulin over intact proinsulin by the insulin secretory granule Type 2 endopeptidase. J Biol Chem, 1992, 267, 22719-22727.
48. Yanagita M, Hoshino H, Nakayama K. Processing of mutated proinsulin with tetrabasic cleavage sites to mature insulin reflects the expression of furin in nonendocrine cell lines. Endocrinology, 1993, 133, 639-644.
49. Groskreutz DJ, Sliwkowski MX, Gorman CM. Genetically engineered proinsulin constitutively processed and secreted as mature, active insulin. J Biol Chem, 1994, 269, 6241-6245.
50. Mojsov S, Heinrich G, Wilson IB, Ravazzola M, Orci L, Habener JF. Reproglucagon gene expression in pancreas and intestine diversifies at the level of post-translational processing. J Biol Chem, 1986, 207, 11880-11889.
51. Mojsov S, Weir GC. Habener JF. Insulinotropin : glucagon-like peptide 1 (7-37) co-encoded in the glucagon gene is a potent stimulator of insulin release in the perfused rat pancreas. J Clin Invest, 1987, 79, 616-619.
52. Ørskov C, Bersani M, Johnsen AH, HΔjrup P, Holst JJ. Complete sequences of glucagon-like peptide 1 from human and pig small intestine J Biol Chem, 1989, 264, 12826-12829.
53. Patzelt C, Schiltz E. Conversion of proglucagon in pancreatic alpha cells : The major end products are glucagon and a single peptide, the major proglucagon fragment, that contains two glucagon-like sequences. Proc Natl Acad Sci USA, 1984, 81, 5007-5011.
54. Patzelt C, Tager HS, Carroll RJ, Steiner DF. Identification and processing of proglucagon in pancreatic islets. Nature, 1979, 252, 260-266,
55. Holst JJ, Bersani M, Johnsen AH. Kofod H, Hartmann B, Ørskov C. Proglucagon processing in porcine and human pancreas. J Biol Chem. 1994, 269, 18827-18833.
56. Rouillé Y. Westermark G, Martin SK, Steiner DF. Proglucagon is processed to glucagon by prohormone convertase PC2 in a TC1-6 cells. Proc Natl Acad Sci USA, 1994, 91, 3242-3246.
57. Ørskov C, Holst JJ, Knuhtsen S. Baldissera FG, Poulsen SS, Nielsen OV Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separately from pig small intestine but not pancreas. Endocrinology, 1986, 119, 1467-1475.
58. Birkeland KI, Torjesen PA, Eriksson J, Vaaler S, Groop L. Hyperproinsulinemia of Type 2 diabetes is not present before the development of hyperglycemia. Diabetes Care, 1994, 17, 1307-1310.
59. Ward WK, LaCava EC, Paquette TL, Beard JC, Wallurn BJ, Porte D Jr. Disproportionate elevation of immunoreactive proinsulin in Type 2 (non-insulin-dependent) diabetes mellitus and in experimental insulin resistance. Diabetologia, 1987, 30, 698-702.
60. Nagi DK, Hendra TJ, Ryle AJ et al. The relationships of concentrations of insulin, intact proinsulin and 32-33 split proinsulin with cardiovascular risk factors in- Type 2 (non-insulin-dependent) diabetic subjects. Diabetologia, 1990, 33, 532-537.
61. Bentley AK, Rees DJG, Rizza C, Brownlee GG. Defective propeptide processing of bllod clotting factor IX caused by mutation of arginine to glutamine a position-4. Cell, 1986, 45, 343-348.
62. Brennan SO. Propeptide cleavage : evidence from human proalbumins. Mol Biol Med, 1989, 6, 87-92.
63. Peters T Jr. Intracellular precursoi forms of plasma proteins. their function and possible occurrence in plasma. Clin Chem, 1987, 78, 1060-1066.
64. Steiner DF, Tager HS, Nanjo K, Chan SJ, Rubenstein AH. Familial syndromes of hyperproinsulinemia and hyperinsulinemia with mild diabetes. In : Seriver SR, Beaudet AL, Sly WS, Vallc D, eds. "The Metabolic Basis of Inherited Disease", 7th Edition New York : McGraw-Hill, 1995, 897-904
65. Alarcón C, Leahy JL, Schuppin GT, Rhodes CJ. Increased secretory demand rather than a defect in the proinsulin conversion mechanism causes hyperproinsulinemia in a glucose-infusion rat model of noninsulin-dependent diabetes mellitus. J Clin Invest, 1995, 95, 1032-1039.
66. Rhodes CJ, Alarcón C. What β-cell defect could lead to hyperproinsulinemia in NIDDM ? Some clues from recent advances made in understanding the proinsulin-processing meachanism. Diabetes, 1994, 43, 511-517
67. Alarcón C, Lincoln B. Rhodes CJ. The biosynthesis of the subtilisin-related proprotein convertase PC3. but not that of the PC2 convertase, is regulated by glucose in parallel to proinsulin biosynthesis in rat pancreatic islets. J Biol Chem, 1993, 268, 4276-4780.
68. Martin SK, Carroll R, Benig M, Steiner DF. Regulation by glucose of the biosynthesis of PC2, PC3 and proinsulin in (ob/ob) mouse islets of Langerhans. FEBS Lett, 1994, 356, 279-282
69. Neerman-Arbez M, Cirulli V, Halban PA. Levels of the conversion and endoproteases PC1 (PC3) and PC2 distinguish between insulin-producing pancreatic islet beta cells and non-beta cells. Biochem J, 1994, 300, 57-61.
70. Naggert JK, Fricker LD, Rouillé Y et al. Hyperproinsulinemia in obese fat/fat mice is associated with a point mutation in the carboxypeptidase E gene and reduced carboxypeptidase activity in the pancreatic islets. Nature Genetics, 1995, 10, 135-142.
71. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Fnedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature, 1994, 372, 425-431.
72. O'Rahilly S, Gray H, Krook A et al. Primary defective pro-hormone processing : a novel plurihormonal syndrome. N Engl J Med, 1995, in press