title: Comparative study of somatostatin-human serum albumin fusion proteins and natural somatostatin on receptor binding, internalization and activation.
abstract: Albumin fusion technology, the combination of small molecular proteins or peptides with human serum albumin (HSA), is an effective method for improving the medicinal values of natural small molecular proteins or peptides. However, comparative studies between HSA-fusion proteins or peptides and the parent small molecules in biological and molecular mechanisms are less reported. In this study, we examined the binding property of two novel somatostatin-HSA fusion proteins, (SST14)2-HSA and (SST28)2-HSA, to human SSTRs in stably expressing SSTR1-5 HEK 293 cells; observed the regulation of receptor internalization and internalized receptor recycling; and detected the receptors activation of HSA fusion proteins in stably expressing SSTR2- and SSTR3-EGFP cells. We showed that both somatostatin-HSA fusion proteins had high affinity to all five SSTRs, stimulated the ERK1/2 phosphorylation and persistently inhibited the accumulation of forskolin-stimulated cAMP in SSTR2- and SSTR3-expressing cells; but were less potent than the synthetic somatostatin-14 (SST-14). Our experiments also showed that somatostatin-HSA fusion proteins did not induce the receptors internalization; rather, they accelerated the recycling of the internalized receptors induced by SST-14 to the plasma membrane. Our results indicated that somatostatin-HSA fusion proteins, different from SST-14, exhibit some particular properties in binding, regulating, and activating somatostatin receptors.
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Deng
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
authors.forename: Yuedi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
authors.forename: Quancheng
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China ; The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Yang
authors.affiliation: Wuxi Second People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
mesh_terms: D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D008024:Ligands; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012709:Serum Albumin / Q000235:genetics; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D008024:Ligands; D017481:Receptors, Somatostatin; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; C103631:somatostatin receptor 3; D013004:Somatostatin; C093733:somatostatin receptor 2; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases