Disease relevance of SPINK1

• CONCLUSIONS: Mechanisms other than the conformational change of PSTI associated with amino-acid substitution, such as abnormal splicing, may underlie the predisposition to pancreatitis in patients with the N34S mutation [1].
• Production of recombinant human pancreatic secretory trypsin inhibitor by Escherichia coli [2].
• Radioimmunoassay for human pancreatic secretory trypsin inhibitor: measurement of serum pancreatic secretory trypsin inhibitor in normal subjects and subjects with pancreatic diseases [3].
• In this study, we tested the hypothesis that the E32del genetic variant of mesotrypsin might represent a risk factor for the development of chronic pancreatitis, as a result of enhanced degradation of pancreatic secretory trypsin inhibitor [4].
• Pancreatic secretory trypsin inhibitor (PSTI) immunoreactivity was detected by a radioimmunoassay in a serum-free culture medium conditioned by a human pancreatic adenocarcinoma cell line, CAPAN-1 [5].

High impact information on SPINK1

• Kinetic studies showed that the binding of 125I-PSTI to 3T3 Swiss albino cells reached the maximum level within 120 min at 4 degrees C, with a slow dissociation rate [6].
• These results indicated that the biological effect of PSTI was mediated by high affinity plasma membrane receptors, which were not a cell-surface proteinase(s) [6].
• Treatment of surface-bound radiolabeled PSTI with a chemical crosslinker (disuccinimidyl suberate) led to the identification of a membrane polypeptide of Mr 140,000 to which PSTI was crosslinked [6].
• Specific binding sites for human pancreatic secretory trypsin inhibitor (PSTI) on 3T3 Swiss albino cells were studied using radioiodinated recombinant PSTI [6].
• Various protease inhibitors had no or only a little effect, and mercaptoethanol and dithiothreitol strongly decreased the binding of 125I-PSTI [6].

Biological context of SPINK1

• pH and temperature effects on the molecular conformation of the porcine pancreatic secretory trypsin inhibitor as detected by hydrogen-1 nuclear magnetic resonance [7].
• The amino acid sequence of canine PSTI was determined by conventional methods [8].
• Functional analysis of recombinant pancreatic secretory trypsin inhibitor protein with amino-acid substitution [1].
• The activity of PSTI protein with a point mutation of the most common type: (34)Asn (AAT)-to-Ser (AGT)(101A>G N34S: N34S) in exon 3, was compared with that of the wild type [1].

Anatomical context of SPINK1

• Pancreatic secretory trypsin inhibitor (PSTI) was purified from canine pancreatic juice by HPLC [8].
• Purification and characterization of pancreatic secretory trypsin inhibitor in human gastric mucosa [9].
• Binding of the bovine and porcine pancreatic secretory trypsin inhibitor (Kazal) to human leukocyte elastase: a thermodynamic study [10].
• Pancreatic secretory trypsin inhibitor immunoreactivity detected in serum-free culture medium of human pancreatic carcinoma cell line, CAPAN-1 [5].
• Isolation in a 55% yield of the low molecular weight pancreatic secretory trypsin inhibitor was achieved by gel filtration of an acid extract of whole inactive rat pancreas juice on Sephadex G-50 at pH 2.5 followed by desalting and ion-exchange chromatography on SP Sephadex C-50 at pH 4 [11].

Associations of SPINK1 with chemical compounds

• Incubation at 37 degrees C resulted in rapid internalization of cell-bound 125I-PSTI, followed by the appearance of trichloroacetic acid-soluble 125I-radioactivity in the culture medium, due to degradation of internalized PSTI [6].
• Binding of the bovine pancreatic secretory trypsin inhibitor (Kazal) to bovine serine (pro)enzymes [12].
• Such an analysis allows to dissect the contributions due to the primary recognition subsite, where small mono-functional ligands (e.g., n-butylamine) bind, from those of the secondary subsite(s), which are additional recognition clefts for macromolecular inhibitors (e.g., BPTI and PSTI) [13].

Other interactions of SPINK1

• Three-dimensional structure of the complexes between bovine chymotrypsinogen A and two recombinant variants of human pancreatic secretory trypsin inhibitor (Kazal-type) [14].
• Binding of porcine pancreatic secretory trypsin inhibitor to bovine beta-trypsin: a kinetic study [15].

Analytical, diagnostic and therapeutic context of SPINK1

• A reliable radioimmunoassay (RIA) for human pancreatic secretory trypsin inhibitor (PSTI) has been developed [3].
• Immunoreactive pancreatic secretory trypsin inhibitor (PSTI) was purified to homogeneity from human gastric mucosa by gel chromatography, ion-exchange chromatography, and repeated reverse-phase high-performance liquid chromatography (HPLC) [9].
• Finally, rHu-PSTI was purified by affinity chromatography on a bovine trypsin-CH-Sepharose 4B column [2].

References