Somatostatin Receptor 2 Phosphorylation Assays
The somatostatin receptor 2 (SST2) is highly expressed in many endocrine cell types and exerts potent inhibitory actions on hormone secretion. It is the primary target for octreotide (Sandostatin) and lanreotide (Somatuline) which are the first line medical treatment for growth hormone (GH)-producing adenomas (acromegaly) and gastrointestinal neuroendocrine tumors (NET). SST2 is a prototypical GPCR for the development of peptide-based radiopharmaceuticals, which are used for imaging of human tumors as well as for peptide receptor radionuclide therapy (PRRT). SST2 desensitization, β-arrestin recruitment and internalization are regulated by phosphorylation of carboxyl-terminal serine341/serine343 (pS341/pS343-SST2), threonine353/threonine354 (pT353/pT354-SST2) and threonine356/threonine359 (pT356/pT359-SST2) residues. This nomenclature refers to the human SST2. This phosphorylation motif is highly conserved across mouse, rat and human. High-efficacy agonists such as octreotide, lanreotide, veldoreotide and SRIF induce rapid phosphorylation of all six sites which is mediated by GRK2 and GRK3. Low-efficacy agonists such as pasireotide induce primarily phosphorylation of S341/S343. S343 is also a substrate for phosphorylation by PKC. SST2 dephosphorylation is primarily mediated by protein phosphatase 1 beta (PP1β). For more information on SST2 pharmacology please refer to the IUPHAR database. For further reading refer to:
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