Molecular and cellular regulation of prohormone processing

Seminars in Cell and Developmental Biology

Volumn 9, Issue 1, 1998, Pages 3-10

  Creemers, John W M ^a   Jackson, Robert S ^b   Hutton, John C ^c  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b ADDENBROOKE S HOSPITAL   (United Kingdom)

^c UNIVERSITY OF COLORADO DENVER   (United States)

Author keywords

Furin; PC1; PC2; Prohormone convertase (pc); Secretion; Sorting; Subtilisin

Indexed keywords

FURIN; HORMONE; PROTEIN PRECURSOR; SUBTILISIN;

AMINO ACID SEQUENCE; CHEMISTRY; GENETICS; METABOLISM; MOLECULAR GENETICS; PROTEIN CONFORMATION; PROTEIN PROCESSING; REVIEW;

AMINO ACID SEQUENCE; FURIN; HORMONES; MOLECULAR SEQUENCE DATA; PROTEIN CONFORMATION; PROTEIN PRECURSORS; PROTEIN PROCESSING, POST-TRANSLATIONAL; SUBTILISINS;

EID: 0031994806     PISSN: 10849521     EISSN: None     Source Type: Journal    
DOI: 10.1006/scdb.1997.0195     Document Type: Article

References (79)

1. Hutton JC (1991) Subtilisin-like proteinases involved in the activation of proproteins of the eukaryotic secretory pathway. Curr Opin Cell Biol 2:1131-1142
2. Steiner DF, Smeekens SP, Ohagi S, Chan SJ (1992) The new enzymology of precursor processing endoproteases. J Biol Chem 276:23435-23438
3. Halban PA, Irminger J-C (1994) Sorting and processing of secretory proteins. Biochem J 299:1-18
4. Seidah NG, Chrétien M, Day R (1994) The family of subtilisin/kexin like pro-protein and pro-hormone convertases: Divergent or shared functions. Biochemie 76:197-209
5. Siezen RJ, Creemers JW, Van de Ven WJ (1994) Homology modelling of the catalytic domain of human furin. A model for the eukaryotic subtilisin-like proprotein convertases. Eur J Biochem 222:255-266
6. Guest PC, Arden SD, Bennett DL, Clark A, Rutherford NG, Hutton JC (1992) The post-translational processing and intracellular sorting of PC2 in the islets of Langerhans. J Biol Chem 267:22401-22406
7. Lindberg I, Ahn SC, Breslin MB (1994) Cellular distributions of the prohormone processing enzymes PC1 and PC2. Mol Cell Neurosci 5:614-622
8. Malide D, Seidah NG, Chrétien M, Bendayan M (1995) Electron microscopic immunocytochemical evidence for the involvement of the convertases PC1 and PC2 in the processing of proinsulin in pancreatic β-cells. Histochem Cytochem 43:11-19
9. Davidson HW, Rhodes CJ, Hutton JC (1988) Intraorganellar Ca and pH control proinsulin cleavage in the pancreatic β cell via two distint site-specific endopeptidases. Nature 333:93-96
10. Bailyes EM, Hutton JC (1992) Kinetic analysis of the type 1 proinsulin endopeptidase using a monoclonal antibody-based immunoabsorbent assay. Biochem J 286:223-229
11. Bailyes EM, Shennan KIJ, Smeekens SP, Steiner DF, Hutton JC, Docherty KD (1992) A member of the eukaryotic subtilisin family (PC3) has the enzymic properties of the type 1 proinsulin-converting endopeptidase. Biochem J 285:391-394
12. Bailyes EM, Shennan KIJ, Usac EF, Arden SD, Guest PC, Docherty K, Horan JC (1995) Differences between the catalytic properties of recombinant human PC2 and endogenous rat PC2. Biochem J 309:587-594
13. Bosshart H, Humphrey J, Deignan E, Davidson J, Drazba J, Yuan L, Oorschot V, Peters PJ, Bonifacino JS (1994) The cytoplasmic domain mediates localization of furin to the trans-Golgi Network en route to the endosomal/lysosomal system. J Cell Biol 126:1157-1172
14. Molloy SS, Thomas L, Slyke JKV, Sternberg PE, Thomas G (1994) Intracellular traffiking and activation of the furin proprotein convertase: localisation to the TGN and recycling from the cell surface. EMBO J 13:18-33
15. Schäfer W, Stroh A, Berghöfer S, Seiler J, Vey M, Kruse ML, Kern HF, Klenk HD, Garten W (1995) Two independent targeting signals in the cytoplasmic domain determine trans-Golgi network localization and endosomal trafficking of the proprotein convertase furin. EMBO J 14:2424-2435
16. Bennett D, Hutton JC (1994) Proinsulin-processing endopeptidases and diabetes, in Molecular Biology of Diabetes, Autoimmunity and Genetics; Insulin Synthesis and Secretion (Draznin B, Leroith D, eds) pp 213-248. Humana Press, New York
17. Farhadi H, Pareek S, Day R, Kurzik-Dumke V, Rentrop M, Galeff EA, Leunissen JA, Van den Ven WJ (1997) Prohormone convertases in mouse submandibular gland: co-localization of furin and nerve growth factor. J Histochem Cytochem 45:795-804
18. Roebroek AJM, Creemers JWM, Pauli IGL, Kurzik-Dumke V, Rentrop M, Galeff EA, Leunissen JA, Ven den Ven WJ (1992) Cloning and functional expression of Dfurin2, a subtilisin-like proprotein processing enzyme of Drosaphila melanogaster with multiple repeats of a cysteine motif. J Biol Chem 267:17208-17215
19. Vey M, Schäfer W, Berghöfer S, Klenk H-D, Garten W (1994) Maturation of the trans-Golgi Network protease furin: Compartmentalization of propeptide removal, substrate cleavage, and COOH-terminal truncation. J Cell Biol 127:1829-1842
20. Leduc R, Molloy SS, Thorne BA, Thomas G (1992) Activation of human furin precursor processing endoprotease occurs by an intramolecular autoproteolytic cleavage. J Biol Chem 267:14304-14308
21. Creemers JWM, Siezen RJ, Roebroek AJM, Ayoubi TAY, Huylebroeck D, Ven WJMVd (1993) Modulation of furin-mediated proprotein processing by site-directed mutagenesis. J Biol Chem 268:21826-21834
22. Anderson ED, VanSlyke JK, Thulin CD, Jean F, Thomas G (1997) Activation of the furin endoprotease is a multiple-step process: requirements for acidification and internal propeptide cleavage. EMBO J 16(7):1508-1518
23. Goodman LJ, Gorman CM (1994) Autoproteolytic activation of the mouse prohormone convertase mPC1. Biochem Biophys Res Commun 201:795-804
24. Matthews G, Shennan KI, Seal AJ, Taylor NA, Colman A, Docherty K (1994) Autocatalytic maturation of the prohormone convertase PC2. J Biol Chem 269:588-592
25. Shennan KIJ, Taylor NA, Jermany JL, Matthews G, Docherty K (1995) 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 270:1402-1497
26. Zhou A, Mains RE (1994) Endoproteolytic processing of proopiomelanocortin and prohormone convertases 1 and 2 in neuroendocrine cells overexpressing prohormone convertases 1 or 2. J Biol Chem 269:17440-17447
27. Creemers JW, Usac EF, Bright NA, Van de Loo JW, Jansen E, Van de Ven WJM, Huttan JC (1996) Identification of a transferable sorting domain for the regulated pathway in the prohormone convertase PC2. J Biol Chem 271:25284-25291
28. Braks JA, Martens GJ (1994) 7B2 is a neuroendocrine chaperone that transiently interacts with prohormone convertase PC2 in the secretory pathway. Cell 78:263-273
29. Zhu X, Lamango NS, Lindberg I (1996) Involvement of a polyproline helix-like structure in the interaction of 7B2 with prohormone convertase 2. J Biol Chem 271:23582-23587
30. Zhu X, Muller L, Mains RE, Lindberg I (1997) Structural elements of PC2 required for interactions with its helper protein 7B2. J Biol Chem 273:1158-1164
31. Benjannet S, Lusson J, Hamelin J, Savaria D, Chretien M, Seidah NG (1995) Structure-function studies on the biosynthesis and bioactivity of the precursor convertase PC2 and the formation of the PC2/7B2 complex. FEBS Lett 362:151-155
32. Martens GJ, Braks JA, Eib DW, Zhou Y, Lindberg I (1994) The neuroendocrine polypeptide 7B2 is an endogenous inhibitor of prohormone convertase PC2. Proc Natl Acad Sci USA 91:5784-5787
33. Horssen AMV, Hurk WHVd, Bailyes EM, Hutton JC, Martens GJM, Lindberg I (1995) Identification of the region within the neuroendocrine polypeptide 7B2 responsible for the inhibition of prohormone convertase PC2. J Biol Chem 270:14292-14296
34. Zhu X, Rouille Y, Lamango NS, Steiner DF, Lindberg I (1996) Internal cleavage of the inhibitory 7B2 carboxyl-terminal peptide by PC2: a potential mechanism for its inactivation. Proc Natl Acad Sci USA 93:4919-4924
35. Siezen RJ, Leunissen JA (1997) Subtilases: the superfamily of subtilisin-like serine proteases. Protein Sci 6:501-523
36. Zhou A, Paquet L, Mains RE (1995) Structural elements that direct specific processing of different mammalian subtilisin-like prohormone convertases. J Biol Chem 270:21509-21516
37. Bryan P, Pantoliano MW, Quill SG, Hsiao HY, Poulos T (1986) Site-directed mutagenesis and the role of the oxyanion hole in subtilisin. Proc Natl Acad Sci USA 83:3743-3745
38. Brenner C, Bevan A, Fuller RS (1994) Biochemical and genetic methods for analyzing specificity and activity of a precursor-processing enzyme: yeast Kex2 protease, kexin. Methods Enzymol 244:152-167
39. Lipkind G, Gong Q, Steiner DF (1995) Molecular modeling of the substrate specificity of prohormone convertases SPC2 and SPC3. J Biol Chem 270:13277-13284
40. Shilton BH, Thomas DY, Cygler M (1997) Crystal structure of Kex1deltap, a prohormone-processing carboxypeptidase from Saccharomyces cerevisiae. Biochemistry 36:9002-9012
41. Ballinger MD, Tom J, Wells JA (1995) Designing subtilisin BPN' to cleave substrates containing dibasic residues. Biochemistry 34:13312-13319
42. Doolittle R (1985) The genealogy of some recently evolved vertebrate proteins. Trends Biochem Sci 10:233-237
43. Hatsuzawa K, Murakami K, Nakayama K (1992) Molecular and enzymatic properties of furin, a Kex2-like endoprotease involved in precursor cleavage at Arg-X-Lys/Arg-Arg sites. J Biochem 111:296-301
44. Gluschankof P, Fuller RS (1994) A C-terminal domain conserved in precursor processing proteases is required for intramolecular N-terminal maturation of pro-Kex2 protease. EMBO J 13:2280-2288
45. Creemers JWM, Vey M, Schäfer W, Ayoubi TA, Roebroek AJ, Klenk HD, Garten W, Van de Ven WJ (1995) Endoproteolytic cleavage of its propeptide is a prerequisite for efficient transport of furin out of the endoplasmic reticulum. J Biol Chem 270:2695-2702
46. Taylor NA, Shennan KI, Cutler DF, Docherty K (1997) Mutations within the propeptide, the primary cleavage site or the catalytic site, or deletion of C-terminal sequences, prevents secretion of proPC2 from transfected COS-7 cells. Biochem J 321:367-373
47. Smeekens SP, Avruch AS, LaMendola J, Chan SJ, Steiner DF (1991) Identification of a cDNA encoding a second putative prohormone convertase related to PC2 in AtT-20 cells and islets of Langerhans. Proc Natl Acad Sci USA 88:340-344
48. Mitra A, Song L, Fricker LD (1994) The C-terminal region of carboxypeptidase E is involved in membrane binding and intracellular routing in AtT-20 cells. J Biol Chem 269:19876-19881
49. Shennan KI, Taylor NA, Docherty K (1994) Calcium- and pH-dependent aggregation and membrane association of the precursor of the prohormone convertase PC2. J Biol Chem 269:18646-18650
50. Hill RM, Ledgerwood EC, Brennan SO, Pu LP, Loh YP, Christie DL, Birch NP (1995) Comparison of the molecular forms of the Kex2/subtilisin-like serine proteases SPC2, SPC3, and furin in neuroendocrine secretory vesicles reveals differences in carboxyl-terminus truncation and membrane association. J Neurochem 65:2318-2326
51. Guest PC, Pipeleers D, Rossier J, Rhodes CJ, Hutton JC (1989) Co-secretion of carboxypeptidase H and insulin from isolated rat islets of Langerhans. Biochem J 264:503-508
52. Zhou Y, Rovere C, Kitabgi P, Lindberg I (1995) Mutational analysis of PC1 (SPC3) in PC12 cells. 66-kDa PC1 is fully functional. J Biol Chem 270:24702-24706
53. Jutras I, Seidah NG, Reudelhuber TL, Brechler V (1997) Two activation states of the prohormone convertase PC1 in the secretory pathway. J Biol Chem 272:15184-15188
54. Cool DR, Normant E, Shen F, Chen HC, Pannell L, Zhang Y, Loh YP (1997) Carboxypeptidase E is a regulated secretory pathway sorting receptor: genetic obliteration leads to endocrine disorders in Cpe(fat) mice. Cell 88:73-83
55. Chanat E, Huttner WB (1991) Milieu-induced, selective aggregation of regulated secretory proteins in the trans-Golgi network. J Cell Biol 115:1505-1519
56. Ward WK, LaCava EC, Paquette TL, Beard JC, Wallum BJ, Jr. DP (1987) Disproportionate elevation of immunoreactive proinsulin in type 2 (non-insulin dependent) diabetes mellitus and in experimental insulin resistance. Diabetologia 30:698-702
57. Temple RC, Carrington CA, Luzio SD, Owens DR, Schneider AE, Sokey WJ, Hales CN (1989) Insulin deficiency in non-insulin dependent diabetes. Lancet 1:293-295
58. Heaton DA, Millward BA, Gray P, Tun Y, Hales CN, Pyke DA, Leslie RD (1987) Evidence of cell dysfunction which does not lead to diabetes: a study of identical twins of insulin dependent diabetes. Br Med J 294:145-146
59. Rhodes CJ, Alarcon C (1994) What beta-cell defect could lead to hyperproinsulinemia in NIDDM? Some clues from recent advances made in understanding the proinsulin-processing. Diabetes 43:511-517
60. Gadot M, Ariav Y, Cerasi E, Kaiser N, Gross DJ (1995) Hyperproinsulinemia in the diabetic Psammomys obesus is a result of increased secretory demand on the beta-cell. Endocrinology 136:4218-4223
61. Rubenstein AH, Block MB, Starr J, Melani F, Steiner DF (1972) Proinsulin and C-peptide in blood. Diabetes 21:661-672
62. Shibasaki Y, Kawakami T, Kanazawa Y, Akanuma Y, Takaku F (1985) Posttranslational cleavage of proinsulin is blocked by a point mutation in familial hyperproinsulinaemia. J Clin Invest 89:1902-1907
63. Yano H, Kitano N, Morimoto M, Polonsky KS, Imura H, Seino Y (1987) A novel point mutation in the human insulin gene giving rise to hyperproinsulinaemia. Proc Natl Acad Sci USA 84:2194-2197
64. Roder ME, Vissing H, Nauck MA (1996) Hyperproinsulinemia in a three-generation Caucasian family due to mutant proinsulin (Arg65-His) not associated with impaired glucose tolerance: the contribution of mutant proinsulin to insulin bioactivity. J Clin Endocrinol Metab 81:1634-1640
65. Chan SJ, Seino S, Gruppuso PA, Schwartz R, Steiner DF (1987) A mutation in the B-chain coding region is associated with impaired proinsulin conversion in a family with hyperproinsulinaemia. Proc Natl Acad Sci USA 84:2194-2197
66. Brennan SO, Nakayama K (1994) Furin has the proalbumin substrate specificity and serpin inhibitory properties of an in situ hepatic convertase. FEBS Lett 338:147-151
67. Brennan SO, Owen MC, Boswell DR, Lewis JH, Carrell RW (1984) Circulating proalbumin associated with a variant proteinase inhibitor. Biochim Biophys Acta 802:24-28
68. Rhodes CJ, Brennan SO, Hutton JC (1989) Proalbumin to albumin conversion by a proinsulin processing endopeptidase of insulin secretory granules. J Biol Chem 264:14240-14245
69. Naggert JK, Fricker LD, Varlamov O, Nishina PM, Rosille Y, Steiner DF, Carroll RJ, Paigen BJ, Leiter EH (1995) Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity. Nat Genet 10:135-142
70. Fricker LD, Berman YL, Leiter EH, Devi LA (1996) Carboxypeptidase E activity is deficient in mice with the fat mutation. Effect on peptide processing. J Biol Chem 271:30619-30624
71. Cain BM, Wang W, Beinfeld MC (1997) Cholecystokinin (CCK) levels are greatly reduced in the brains but not the duodenums of Cpe(fat)/Cpe(fat) mice: a regional difference in the involvement of carboxypeptidase E (Cpe) in pro-CCK processing. Endocrinology 138:4034-4037
72. Song L, Fricker LD (1995) Purification and characterization of carboxypeptidase D, a novel carboxypeptidase E-like enzyme, from bovine pituitary. J Biol Chem 270:25007-25013
73. Jackson RS, Creemers JW, Ohagi S, Raffin-Sansan ML, Sanders L, Montague CT, Hutton JC, O'Rahilly S (1997) Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 16:303-306
74. O'Rahilly S, Gray H, Humphreys PJ, Krooks A, Polansky KS, White A, Gibson S, Taylor K, Carr C (1995) Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. N Engl J Med 333:1386-1390
75. Azaryan AV, Wong M, Friedman TC, Cawley NX, Estivariz FE, Chen HC, Loh YP (1993) Purification and characterization of a paired basic residue-specific yeast aspartic protease encoded by the YAP3 gene. Similarity to the mammalian proopiomelanocortin-converting enzyme. J Biol Chem 268:11968-11975
76. Hook VY, Moran K, Kannan R, Kohn A, Lively MO, Azaryan A, Schiller M, Miller K (1997) High-level expression of the prohormones proenkephalin, pro-neuropeptide Y, proopiomelanocortin, and beta-protachykinin for in vitro prohormone processing. Protein Expr Purif 10:80-88
77. Nillni EA, Luo LG, Jackson IM, McMillan P (1996) Identification of the thyrotropin-releasing hormone precursor, its processing products, and its coexpression with convertase 1 in primary cultures of hypothalamic neurons: anatomic distribution of PC1 and PC2. Endocrinology 137:5651-5661
78. Furuta M, Yano H, Zhou A, Rasille Y, Holst JJ, Carroll R, Ravazzola M, Orci L, Furuta, H, Steiner DF (1997) Defective prohormone processing and altered pancreatic islet morphology in mice lacking active Spc2. Proc Natl Acad Sci USA 94:6646-6651
79. Spiegelman BM, Flier JS (1996) Adipogenesis and obesity: rounding out the big picture. Cell 87:377-389