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Fine‐tuning somatostatin receptor signalling by agonist‐selective phosphorylation and dephosphorylation: IUPHAR Review 5
Author(s) -
Schulz Stefan,
Lehmann Andreas,
Kliewer Andrea,
Nagel Falko
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12551
Subject(s) - somatostatin receptor , pasireotide , somatostatin , dephosphorylation , phosphorylation , somatostatin receptor 1 , g protein coupled receptor , receptor , somatostatin receptor 2 , biology , somatostatin receptor 3 , agonist , microbiology and biotechnology , chemistry , biochemistry , endocrinology , phosphatase , hormone , growth hormone , acromegaly
The biological actions of somatostatin are mediated by a family of five GPCRs , named sst 1 to sst 5 . Somatostatin receptors exhibit equally high‐binding affinities to their natural ligand somatostatin‐14 and largely overlapping distributions. The overexpression of somatostatin receptors in human tumours is the molecular basis for diagnostic and therapeutic application of the stable somatostatin analogues octreotide, lanreotide and pasireotide. The efficiency of somatostatin receptor signalling is tightly regulated and ultimately limited by the coordinated phosphorylation and dephosphorylation of intracellular carboxyl‐terminal serine and threonine residues. Here, we review and discuss recent progress in the generation and application of phosphosite‐specific antibodies for human sst 2 and sst 5 receptors. These phosphosite‐specific antibodies are unique tools to monitor the spatial and temporal dynamics of receptors phosphorylation and dephosphorylation. Using a combined approach of phosphosite‐specific antibodies and si RNA knock‐down screening, relevant kinases and phosphatases were identified. Emerging evidence suggests distinct mechanisms of agonist‐selective fine‐tuning for individual somatostatin receptors. The recently uncovered differences in phosphorylation and dephosphorylation of these receptors may hence be of physiological significance in mediating responses to acute, persistent or repeated stimuli in a variety of target tissues.