Disease relevance of Prss7

• Daily administration of cortisone acetate (25 micrograms X g body weight (bw)-1 X day-1), insulin (12.5 mU X g bw-1 X day-1), or epidermal growth factor (4 micrograms X g bw-1 X day-1) during 3 days to 8-day-old mice induced a premature increase of enteropeptidase [1].

High impact information on Prss7

• Enterokinase activity can be induced in epi mice by feeding its substrate trypsinogen, but not by trypsin or chymotrypsinogen [2].
• Polyacrylamide gels containing extracts from control pancreas required prior activation of trypsinogen and chymotrypsinogen (with exogenously added enterokinase and trypsin, respectively) to produce activity staining with specific synthetic substrates [3].
• The longer isoform, which we designated MAT1 and RAT1, has a simple type II transmembrane protein structure, consisting of a short cytoplasmic domain, a transmembrane domain, a SEA (63-kDa sea urchin sperm protein, enteropeptidase, agrin) module, and a serine protease domain [4].
• In contrast, messenger RNA levels of a few immune response, metabolism and protease genes (e.g. Prss7 and Mmp13) were higher in the tolerant C57BL/6 strain as compared to A/J.Genes and Immunity (2006) 7, 667-679. doi:10.1038/sj.gene.6364345; published online 26 October 2006 [5].
• The proteinase portion domain shows 46-53% identity with mouse neurotrypsin, acrosin, hepsin and enteropeptidase [6].

Biological context of Prss7

• To investigate this restricted expression pattern, mouse enterokinase cDNA was cloned, and the distribution of enterokinase mRNA and enzymatic activity were determined in adult mice and during gestation [7].
• Enterokinase (enteropeptidase) is expressed only in proximal small intestine, where it initiates digestive enzyme activation by converting trypsinogen into trypsin [7].
• Finally, we found that cleavage of all nine fusion proteins reflects accurate hydrolysis at the DDDDK(156) and DDDDK(201) sites when recombinant light chain enterokinase was used while non-specific processing at secondary sites were observed when these fusion proteins were treated with the native holoenzyme [8].

Anatomical context of Prss7

• Structure of murine enterokinase (enteropeptidase) and expression in small intestine during development [7].
• Enterokinase mRNA and enzymatic activity were not detected in the duodenum of fetal mice but were easily detected in the duodenum on postnatal days 2-6 [7].
• By in situ mRNA hybridization, enterokinase mRNA was localized to the enterocytes throughout the villus [7].
• Enterokinase activity (a marker for duodenal mucosa) was nearly absent from the duodenum of epi mice [2].

Associations of Prss7 with chemical compounds

• Analysis of enterokinase sequences showed that a mucinlike domain near the NH2 terminus is composed of repeated approximately 15-amino acid Ser/Thr-rich motifs [7].
• Further variants comprising DDDDK(156)SS, DDDDK(156)SD and DDDDK(156)RR showed that the minimal critical determinants for enhanced enterokinase cleavage are serine in the P1' position followed by a serine or a basic residue, lysine or arginine, in the P2' position [8].
• Finally, cortisone acetate which has a major effect on this activity during suckling period was unable to influence adult small intestinal enteropeptidase activity [1].
• Analysis by two-dimensional electrophoresis, using the purified zymogens as substrates, revealed enterokinase isozymes and chymotrypsinogen-activating factors in both the intestinal extract and luminal fluid [9].
• Thyroxine alone (1 microgram X g bw-1 X day-1) had no significant effect on enteropeptidase activity [1].

Analytical, diagnostic and therapeutic context of Prss7

• By Northern blotting and trypsinogen activation assays, enterokinase mRNA and enzymatic activity were undetectable in stomach, abundant in duodenum, and decreased distally until they were undetectable in midjejunum, ileum, and colon [7].
• The hydrophilic transmembrane envelope protein was purified by one-step Ni-NTA affinity chromatography and then the fusion tag consisting of the six-histidine peptide and S peptide was removed by cleavage with enterokinase [10].

References