A novel A121T mutation in human cationic trypsinogen associated with hereditary pancreatitis: Functional data indicating a loss-of-function mutation influencing the R122 trypsin cleavage site

Journal of Medical Genetics

Volumn 45, Issue 8, 2008, Pages 507-512

  Felderbauer, Peter ^a   Schnekenburger, J ^b   Lebert, R ^a   Bulut, K ^a   Parry, M ^c   Meister, T ^b   Schick, V ^b   Schmitz, F ^a   Domschke, W ^b   Schmidt, W E ^a  

^a ST JOSEF HOSPITAL   (Germany)

^b UNIVERSITY OF MÜNSTER   (Germany)

^c RCC Ltd   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; THREONINE; TRYPSIN; TRYPSINOGEN;

ABDOMINAL PAIN; ADULT; ALCOHOL CONSUMPTION; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ARTICLE; BLOOD SAMPLING; CASE REPORT; CHOLECYSTECTOMY; CHOLELITHIASIS; CHRONIC PANCREATITIS; COMPUTER ASSISTED TOMOGRAPHY; DNA SEQUENCE; ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; ENZYME LINKED IMMUNOSORBENT ASSAY; FLUORESCENCE RESONANCE ENERGY TRANSFER; GENE MUTATION; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; HUMAN; MOLECULAR MODEL; MUTATIONAL ANALYSIS; NUCLEOTIDE SEQUENCE; PANCREATITIS; PEDIGREE ANALYSIS; PHENOTYPE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; RESTRICTION MAPPING;

AMINO ACID SUBSTITUTION; FEMALE; FLUORESCENCE RESONANCE ENERGY TRANSFER; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MALE; MIDDLE AGED; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTATION; PANCREATITIS, CHRONIC; PEDIGREE; PENETRANCE; TRYPSINOGEN;

EID: 50049088249     PISSN: 00222593     EISSN: None     Source Type: Journal    
DOI: 10.1136/jmg.2007.056481     Document Type: Article

References (36)

1. Whitcomb DC, Preston RA, Aston CE, Sossenheimer MJ, Barua PS, Zhang Y, Wong-Chong A, White GJ, Wood PG, Gates LK Jr, Ulrich C, Martin SP, Post JC, Ehrlich GD. A gene for hereditary pancreatitis maps to chromosome 7q35. Gastroenterology 1996;110:1975-80.
2. Le Bodic L, Bignon JD, Raguenes O, Mercier B, Georgelin T, Schnee M, Soulard F, Gagne K, Bonneville F, Muller JY, Bachner L, Férec C. The hereditary pancreatitis gene maps to long arm of chromosome 7. Hum Mol Genet 1996;5:549-54.
3. Pandya A, Blanton SH, Landa B, Javaheri R, Melvin E, Nance WE, Markello T. Linkage studies in a large kindred with hereditary pancreatitis confirms mapping of the gene to a 16-cM region on 7q. Genomics 1996;38:227-30.
4. Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK Jr, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat Genet 1996;14:141-5.
5. Teich N, Rosendahl J, Toth M, Mossner J, Sahin-Toth M. Mutations of human cationic trypsinogen (PRSS1) and chronic pancreatitis. Hum Mutat 2006;27:721-30.
6. Archer H, Jura N, Keller J, Jacobson M, Bar-Sagi D. A mouse model of hereditary pancreatitis generated by transgenic expression of R122H trypsinogen. Gastroenterology 2006;131:1844-55.
7. Le Marechal C, Chen JM, Quere I, Raguenes O, Ferec C, Auroux J. Discrimination of three mutational events that result in a disruption of the R122 primary autolysis site of the human cationic trypsinogen (PRSS1) by denaturing high performance liquid chromatography. BMC Genet 2001;2:19.
8. Simon P, Weiss FU, Sahin-Toth M, Parry M, Nayler O, Lenters B, Schnekenburger J, Mayerle J, Domschke W, Lerch MM. Hereditary pancreatitis caused by a novel PRSS1 mutation (Arg-122 - > Cys) that alters autoactivation and autodegradation of cationic trypsinogen. J Biol Chem 2002;277:5404-10.
9. Pfutzer R, Myers E, Applebaum-Shapiro S, Finch R, Ellis I, Neoptolemos J, Kant JA, Whitcomb DC. Novel cationic trypsinogen (PRSS1) N29T and R122C mutations cause autosomal dominant hereditary pancreatitis. Gut 2002;50:271-2.
10. Chen J, Piepoli Bis A, Le Bodic L, Ruszniewski P, Robaszkiewicz M, Deprez P, Raguenes O, Quere I, Andriulli A, Ferec C. Mutational screening of the cationic trypsinogen gene in a large cohort of subjects with idiopathic chronic pancreatitis. Clin Genet 2001:59:189-93.
11. Sahin-Toth M, Graf L, Toth M. Trypsinogen stabilization by mutation Arg117 - >His: a unifying pathomechanism for hereditary pancreatitis? Biochem Biophys Res Commun 1999;264:505-8.
12. Kukor Z, Toth M, Pal G, Sahin-Toth M. Human cationic trypsinogen. Arg(117) is the reactive site of an inhibitory surface loop that controls spontaneous zymogen activation. J Biol Chem 2002; 277:6111-7.
13. Sahin-Toth M. Hereditary pancreatitis-associated mutation asn(21) - > ile stabilizes rat trypsinogen in vitro. J Biol Chem 1999; 274:29699-704.
14. Felderbauer P, Hoffmann P, Einwachter H, Bulut K, Ansorge N, Schmitz F, Schmidt WE. A novel mutation of the calcium sensing receptor gene is associated with chronic pancreatitis in a family with heterozygous SPINK1 mutations. BMC Gastroenterol 2003:34.
15. Bhatia E, Choudhuri G, Sikora SS, Landt O, Kage A, Becker M, Witt H. Tropical calcific pancreatitis: strong association with SPINK1 trypsin inhibitor mutations. Gastroenterology 2002; 123:1020-5.
16. Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 1997;18:2714-23.
17. Gaboriaud C, Serre L, Guy-Crotte O, Forest E, Fontecilla-Camps JC. Crystal structure of human trypsin 1: unexpected phosphorylation of Tyr151. J Mol Biol 1996;259:995-1010.
18. Matayoshi ED, Wang GT, Krafft GA, Erickson J. Novel fluorogenic substrates for assaying retroviral proteases by resonance energy transfer. Science 1990;247:954-8.
19. Schechter I, Berger A. On the size of the active site in proteases. I. Papain. Biochem Biophys Res Commun 1967; 27:157-62.
20. Sahin-Toth M. Biochemical models of hereditary pancreatitis. Endocrinol Metab Clin North Am 2006;35:303-12, ix.
21. Sahin-Toth M, Toth M. Gain-of-function mutations associated with hereditary pancreatitis enhance autoactivation of human cationic trypsinogen. Biochem Biophys Res Commun 2000;278:286-9.
22. Sahin-Toth M. Human cationic trypsinogen. Role of Asn-21 in zymogen activation and implications in hereditary pancreatitis. J Biol Chem 2000;275:22750-5.
23. Sahin-Toth M. The pathobiochemistry of hereditary pancreatitis: studies on recombinant human cationic trypsinogen. Pancreatology 2001;1:461-5.
24. Howes N, Lerch MM, Greenhalf W, Stocken DD, Ellis I, Simon P, Truninger K, Ammann R, Cavallini G, Charnley RM, Uomo G, Delhaye M, Spicak J, Drumm B, Jansen J, Mountford R, Whitcomb DC, Neoptolemos JP, the European Registry of Hereditary Pancreatitis and Pancreatic Cancer (EUROPAC). Clinical and genetic characteristics of hereditary pancreatitis in Europe. Clin Gastroenterol Hepatol 2004; 2:252-61.
25. Teich N, Ockenga J, Hoffmeister A, Manns M, Mossner J, Keim V. Chronic pancreatitis associated with an activation peptide mutation that facilitates trypsin activation. Gastroenterology 2000; 119:461-5.
26. Teich N, Bauer N, Mossner J, Keim V. Mutational screening of patients with nonalcoholic chronic pancreatitis: identification of further trypsinogen variants. Am J Gastroenterol 2002; 97:341-6.
27. Rosendahl J, Witt H, Szmola R, Bhatia E, Ozsvari B, Landt O, Schulz HU, Gress TM, Pfutzer R, Lohr M, Kovacs P, Blüher M, Stumvoll M, Choudhuri G, Hegyi P, te Morsche RH, Drenth JP, Truninger K, Macek M Jr, Puhl G, Witt U, Schmidt H, Büning C, Ockenga J, Kage A, Groneberg DA, Nickel R, Berg T, Wiedenmann B, Bödeker H, Keim V, Mössner J, Teich N, Sahin-Tóth M. Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis. Nat Genet 2008;40:78-82.
28. Delaage M, Lazdunski M. The binding of Ca2+ to trypsinogen and its relation to the mechanism of activation. Biochem Biophys Res Commun 1967;28:390-4.
29. Schmid RM, Whitcomb DC. Genetically defined models of chronic pancreatitis. Gastroenterology 2006;131:2012-5.
30. Laft SA, Auld DS, Vallee BL. Fluorescence determination of carboxypeptidase A activity based on electronic energy transfer. Anal Biochem 1972;50:56-62.
31. Hallangk W, Lerch MM, Brandt-Nedelev B, Roth W, Ruthenbuerger M, Reinheckel T, Domschke W, Lippert H, Peters C, Deussing J. Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis. J Clin Invest 2000;106:773-81.
32. Halangk W, Kruger B, Ruthenburger M, Sturzebecher J, Albrecht E, Lippert H, Lerch MM. Trypsin activity is not involved in premature, intrapancreatic trypsinogen activation. Am J Physiol Gastrointest Liver Physiol 2002;282:G367-74.
33. Szilagyi L, Kenesi E, Katona G, Kaslik G, Juhasz G, Graf L. Comparative in vitro studies on native and recombinant human cationic trypsins. Cathepsin B is a possible pathological activator of trypsinogen in pancreatitis. J Biol Chem 2001;276:24574-80.
34. Szmola R, Sahin-Toth M. Chymotrypsin C (caldecrin) promotes degradation of human cationic trypsin: identity with Rinderknecht's enzyme Y. Proc Natl Acad Sci USA 2007;104:11227-32.
35. Lerch MM, Gorelick FS. Early trypsinogen activation in acute pancreatitis. Med Clin North Am 2000;84:549-63, viii.
36. Ruthenburger M, Mayerle J, Lerch MM. Cell biology of pancreatic proteases. Endocrinol Metab Clin North Am 2006;35:313-31, ix.