Brakch N, Cohen P, Boileau G
Département de biochimie, Faculté de médecine, Université de Montréal, Quebec, Canada.
Biochem Biophys Res Commun. 1994 Nov 30;205(1):221-9. doi: 10.1006/bbrc.1994.2653.
Somatostatin-14 (S-14) and somatostatin-28 (S-28) are generated by differential processing of a single precursor at a dibasic (R-K) or monobasic (R) proteolytic cleavage site, respectively. To study the pathways of processing of prosomatostatin, we have expressed in AtT20 cells cDNA encoding human prosomatostatin and prosomatostatin mutated in one or the other processing site. Analysis of the peptides present in cell extracts or culture media before and after stimulation of the cells with 8-BrcAMP indicated that prosomatostatin can enter three distinct secretory pathways where it is differently processed: 1) prosomatostatin was secreted through the constitutive pathway; 2) the regulated secretory pathway generated S-14 which was released upon stimulation of the cells with 8-BrcAMP; 3) an alternative pathway, insensitive to 8-BrcAMP produced S-28 and S-14. Moreover, our results suggest that the R-K processing site used to produce S-14 is an important structural feature for targeting the precursor to the regulated secretory pathway.
生长抑素 -14（S -14）和生长抑素 -28（S -28）分别是由单一前体在双碱性（R -K）或单碱性（R）蛋白水解切割位点进行差异性加工产生的。为了研究前生长抑素的加工途径，我们在AtT20细胞中表达了编码人前生长抑素以及在其中一个或另一个加工位点发生突变的前生长抑素的cDNA。在用8 -溴环磷酸腺苷（8 -BrcAMP）刺激细胞前后，对细胞提取物或培养基中存在的肽进行分析表明，前生长抑素可以进入三种不同的分泌途径，在这些途径中它会被不同地加工：1）前生长抑素通过组成型途径分泌；2）受调控的分泌途径产生S -14，在用8 -BrcAMP刺激细胞时释放；3）一条对8 -BrcAMP不敏感的替代途径产生S -28和S -14。此外，我们的结果表明，用于产生S -14的R -K加工位点是将前体靶向到受调控分泌途径的一个重要结构特征。
