Identification of human somatostatin receptor 2 domains involved in internalization and signaling in QGP-1 pancreatic neuroendocrine tumor cell line
Articolo
Data di Pubblicazione:
2016
Citazione:
Identification of human somatostatin receptor 2 domains involved in internalization and signaling in QGP-1 pancreatic neuroendocrine tumor cell line / V. Cambiaghi, E. Vitali, D. Morone, E. Peverelli, A. Spada, G. Mantovani, A.G. Lania. - In: ENDOCRINE. - ISSN 1355-008X. - (2016 Jul), pp. 1-12. [Epub ahead of print] [10.1007/s12020-016-1026-2]
Abstract:
Somatostatin exerts inhibitory effects on hormone secretion and cell proliferation via five receptor subtypes (SST1–SST5), whose internalization is regulated by β-arrestins. The receptor domains involved in these effects have been only partially elucidated. The aim of the study is to characterize the molecular mechanism and determinants responsible for somatostatin receptor 2 internalization and signaling in pancreatic neuroendocrine QGP-1 cell line, focusing on the third intracellular loop and carboxyl terminal domains. We demonstrated that in cells transfected with somatostatin receptor 2 third intracellular loop mutant, no differences in β-arrestins recruitment and receptor internalization were observed after somatostatin receptor 2 activation in comparison with cells bearing wild-type somatostatin receptor 2. Conversely, the truncated somatostatin receptor 2 failed to recruit β-arrestins and to internalize after somatostatin receptor 2 agonist (BIM23120) incubation. Moreover, the inhibitory effect of BIM23120 on cell proliferation, cyclin D1 expression, P-ERK1/2 levels, apoptosis and vascular endothelial growth factor secretion was completely lost in cells transfected with either third intracellular loop or carboxyl terminal mutants. In conclusion, we demonstrated that somatostatin receptor 2 internalization requires intact carboxyl terminal while the effects of SS on cell proliferation, angiogenesis and apoptosis mediated by somatostatin receptor 2 need the integrity of both third intracellular loop and carboxyl terminal.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
pancreatic neuroendocrine tumors; Somatostatin 2 receptor subtype; Somatostatin receptor; β-arrestins; endocrinology, diabetes and Metabolism; endocrinology
Elenco autori:
V. Cambiaghi, E. Vitali, D. Morone, E. Peverelli, A. Spada, G. Mantovani, A.G. Lania
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