Schiesser M, Bimmler D, Frick T W, Graf R
Pankreatitis-Forschungslabor, Departement Chirurgie, Universitätsspital Zürich, Switzerland.
Pancreas. 2001 Mar;22(2):186-92. doi: 10.1097/00006676-200103000-00012.
Pancreatitis-associated protein (PAP), a secretory acute-phase protein of the pancreatic acinar cell, is highly up-regulated early in acute pancreatitis. PAP expression returns to undetectable levels when the pancreas recovers. In the rat, three isoforms of PAP are known, all of which are upregulated during acute pancreatitis. Their functions remain obscure. Pancreatic stone protein (PSP/reg), which shows strong sequence homology to PAP, is secreted into pancreatic juice under physiologic and pathologic conditions. PSP/reg is highly susceptible to trypsin cleavage at its ARG11-ILE12 bond. Cleavage results in an N-terminal undecapeptide and a C-terminal peptide called pancreatic thread protein (PTP). PTP forms oligomeric fibrillar structures, which spontaneously sediment in vitro. PTP can be found in protein plugs or stones from patients with chronic pancreatitis. Rat PAP contains a trypsin cleavage site at the same position as PSP/reg. We hypothesize that PAP is susceptible to tryptic cleavage, and that the C-terminal cleavage product of PAP spontaneously precipitates at neutral pH. To test our hypothesis, we generated and purified recombinant PAP. Here we report the production of rat PAP I, II, and III in a yeast expression system using Pichia pastoris. We demonstrate in vitro the tryptic cleavage of rat PAP and the formation of a spontaneously precipitating peptide, which we call pancreatitis-associated thread protein (PATP). PATP displays pH-dependent solubility characteristics very similar to those of PTP.
胰腺炎相关蛋白（PAP）是胰腺腺泡细胞分泌的一种急性期蛋白，在急性胰腺炎早期高度上调。胰腺恢复时，PAP表达恢复到检测不到的水平。在大鼠中，已知PAP有三种同工型，在急性胰腺炎期间均上调，但其功能仍不清楚。胰腺结石蛋白（PSP/reg）与PAP有很强的序列同源性，在生理和病理条件下分泌到胰液中。PSP/reg在其ARG11-ILE12键处极易被胰蛋白酶切割，切割产生一个N端十一肽和一个C端肽，称为胰腺丝蛋白（PTP）。PTP形成寡聚纤维结构，在体外自发沉淀。PTP可在慢性胰腺炎患者的蛋白栓或结石中发现。大鼠PAP在与PSP/reg相同的位置含有一个胰蛋白酶切割位点。我们推测PAP易被胰蛋白酶切割，且PAP的C端切割产物在中性pH下自发沉淀。为验证我们的推测，我们制备并纯化了重组PAP。在此我们报告了利用毕赤酵母在酵母表达系统中生产大鼠PAP I、II和III。我们在体外证明了大鼠PAP的胰蛋白酶切割以及一种自发沉淀肽的形成，我们将其称为胰腺炎相关丝蛋白（PATP）。PATP表现出与PTP非常相似的pH依赖性溶解性特征。
