Human Cationic Trypsinogen

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Human cationic trypsinogen (PRSS1) variants and chronic pancreatitis.

Variations in the serine protease 1 (PRSS1) gene encoding human cationic trypsinogen have been conclusively associated with autosomal dominant hereditary pancreatitis and sporadic nonalcoholic chronic pancreatitis. Most high-penetrance PRSS1 variants increase intrapancreatic trypsin activity by stimulating trypsinogen autoactivation and/or by inhibiting chymotrypsin C-dependent trypsinogen degr...

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Chymotrypsin C (caldecrin) stimulates autoactivation of human cationic trypsinogen.

Trypsin-mediated trypsinogen activation (autoactivation) facilitates digestive zymogen activation in the duodenum but may precipitate pancreatitis if it occurs prematurely in the pancreas. Autoactivation of human cationic trypsinogen is inhibited by a repulsive electrostatic interaction between the unique Asp218 on the surface of cationic trypsin and the conserved tetra-aspartate (Asp19-22) mot...

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Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen

BACKGROUND The R122H mutation of the cationic trypsinogen was found in patients with hereditary pancreatitis. A transgenic animal carrying this mutation could be useful as a genetic model system of pancreatitis. METHODS Mice transgenic for the human R122H cationic trypsinogen were generated using the -205 fragment of the rat elastase promoter. The presence of the transgene was assayed in the ...

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Structural Basis for the Specific Activation of Human Cationic Trypsinogen by Human Enteropeptidase”

Human cationic trypsinogen is activated by human enteropeptidase much more readily than bovine trypsinogen, the ratios k,,,/K,,, being 330 and 11 mr+-’ s’, respectively. Conversely, porcine enteropeptidase activates bovine trypsinoyen much more rapidly (k&K,,, = 630 rnM-‘s-‘) than human cationic trypsinogen (k,,,/K,,, = 2.4 mM-‘s--‘). The primary structure of the activation region of human cati...

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Hereditary pancreatitis caused by mutation-induced misfolding of human cationic trypsinogen: a novel disease mechanism.

We investigated the biochemical properties and cellular expression of the c.346C>T (p.R116C) human cationic trypsinogen (PRSS1) mutant, which we identified in a German family with autosomal dominant hereditary pancreatitis. This mutation leads to an unpaired Cys residue with the potential to interfere with protein folding via incorrect disulfide bond formation. Recombinantly expressed p.R116C t...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 2002

ISSN: 0021-9258

DOI: 10.1074/jbc.m110959200