Graf R, Schiesser M, Scheele G A, Marquardt K, Frick T W, Ammann R W, Bimmler D
Pancreatitis Research Laboratory, Department of Visceral Surgery, University Hospital, Zürich, 8091, Switzerland.
J Biol Chem. 2001 Jun 15;276(24):21028-38. doi: 10.1074/jbc.M010717200. Epub 2001 Mar 16.
A group of 16-kDa proteins, synthesized and secreted by rat pancreatic acinar cells and composed of pancreatic stone protein (PSP/reg) and isoforms of pancreatitis-associated protein (PAP), show structural homologies, including conserved amino acid sequences, cysteine residues, and highly sensitive N-terminal trypsin cleavage sites, as well as conserved functional responses in conditions of pancreatic stress. Trypsin activation of recombinant stress proteins or counterparts contained in rat pancreatic juice (PSP/reg, PAP I and PAP III) resulted in conversion of 16-kDa soluble proteins into 14-kDa soluble isoforms (pancreatic thread protein and pancreatitis-associated thread protein, respectively) that rapidly polymerize into insoluble sedimenting structures. Activated thread proteins show long lived resistance to a wide spectrum of proteases contained in pancreatic juice, including serine proteases and metalloproteinases. In contrast, PAP II, following activation with trypsin or pancreatic juice, does not form insoluble structures and is rapidly digested by pancreatic proteases. Scanning and transmission electron microscopy indicate that activated thread proteins polymerize into highly organized fibrillar structures with helical configurations. Through bundling, branching, and extension processes, these fibrillar structures form dense matrices that span large topological surfaces. These findings suggest that PSP/reg and PAP I and III isoforms consist of a family of highly regulated soluble secretory stress proteins, which, upon trypsin activation, convert into a family of insoluble helical thread proteins. Dense extracellular matrices, composed of helical thread proteins organized into higher ordered matrix structures, may serve physiological functions within luminal compartments in the exocrine pancreas.
一组由大鼠胰腺腺泡细胞合成并分泌的16 kDa蛋白，由胰石蛋白（PSP/reg）和胰腺炎相关蛋白（PAP）的同工型组成，它们具有结构同源性，包括保守的氨基酸序列、半胱氨酸残基和高度敏感的N端胰蛋白酶切割位点，以及在胰腺应激条件下保守的功能反应。重组应激蛋白或大鼠胰液中所含对应物（PSP/reg、PAP I和PAP III）的胰蛋白酶激活导致16 kDa可溶性蛋白转化为14 kDa可溶性同工型（分别为胰线蛋白和胰腺炎相关线蛋白），它们迅速聚合成不溶性沉淀结构。活化的线蛋白对胰液中包含的多种蛋白酶具有长期抗性，包括丝氨酸蛋白酶和金属蛋白酶。相比之下，PAP II在用胰蛋白酶或胰液激活后不会形成不溶性结构，并会迅速被胰腺蛋白酶消化。扫描电子显微镜和透射电子显微镜表明，活化的线蛋白聚合成具有螺旋构型的高度有序的纤维状结构。通过捆绑、分支和延伸过程，这些纤维状结构形成跨越较大拓扑表面的致密基质。这些发现表明，PSP/reg以及PAP I和III同工型由一类高度调控的可溶性分泌应激蛋白组成，它们在胰蛋白酶激活后会转化为一类不溶性螺旋线蛋白。由组织成更高阶基质结构的螺旋线蛋白组成的致密细胞外基质，可能在外分泌胰腺的管腔隔室内发挥生理功能。
