Herpesviruses are enveloped by a lipid bilayer that contains at least a dozen glycoproteins. The virion surface glycoproteins mediate recognition of susceptible cells and promote fusion of the viral envelope with the cell membrane, leading tovirus entry. No single glycoprotein associated with the virion membrane has been identified as the fusogen [].Glycoprotein L (gL) forms a non-covalently linked heterodimer with glycoprotein H (gH). This heterodimer is essential for virus-cell and cell-cell fusion since the association of gH and gL is necessary for correct localisation of gH to the virion or cell surface. gH anchoring the heterodimer to the plasma membrane through its transmembrane domain. gL lacks a transmembrane domain and is secreted from cells when expressed in the absence of gH [].This entry represents Herpesvirus glycoprotein L (gL), which is a virion associated envelope glycoprotein []. Heterodimer formation between gH and gL has been demonstrated in both virions and infected cells []. Heterodimer formation between gL and gH is important for the proper folding of gH and its insertion into the membrane because the anti-gH conformation-dependent monoclonal antibodies (mAbs) 53S and LP11 bind gH only when gL is present [, ].
Herpesviruses are enveloped by a lipid bilayer that contains at least a dozen glycoproteins. The virion surface glycoproteins mediate recognition of susceptible cells and promote fusion of the viral envelope with the cell membrane, leading to virus entry. No single glycoprotein associated with the virion membrane has been identified as the fusogen [].Glycoprotein L (gL) forms a non-covalently linked heterodimer with glycoprotein H (gH). This heterodimer is essential for virus-cell and cell-cell fusion since the association of gH and gL is necessary for correct localisation of gH to the virion or cell surface. gH anchoring the heterodimer to the plasma membrane through its transmembrane domain. gL lacks a transmembrane domain and is secreted from cells when expressed in the absence of gH [].This entry represents Herpesvirus glycoprotein L (gL), which is a virion associated envelope glycoprotein []. Heterodimer formation between gH and gL has been demonstrated in both virions and infected cells []. Heterodimer formation between gL and gH is important for the properfolding of gH and its insertion into the membrane because the anti-gH conformation-dependent monoclonal antibodies (mAbs) 53S and LP11 bind gH only when gL is present [, ].
Herpesviruses are enveloped by a lipid bilayer that contains at least a dozen glycoproteins. The virion surface glycoproteins mediate recognition of susceptible cells and promote fusion of the viral envelope with the cell membrane, leading to virus entry. No single glycoprotein associated with the virion membrane has been identified as the fusogen [].Glycoprotein L (gL) forms a non-covalently linked heterodimer with glycoprotein H (gH). This heterodimer is essential for virus-cell and cell-cell fusion since the association of gH and gL is necessary for correct localisation of gH to the virion or cell surface. gH anchoring the heterodimer to the plasma membrane through its transmembrane domain. gL lacks a transmembrane domain and is secreted from cells when expressed in the absence of gH [].This entry represents Herpesvirus glycoprotein L (gL), which is a virion associated envelope glycoprotein []. Heterodimer formation between gH and gL has been demonstrated in both virions and infected cells []. Heterodimer formation between gL and gH is important for the proper folding of gH and its insertion into the membrane because the anti-gH conformation-dependent monoclonal antibodies (mAbs) 53S and LP11 bind gH only when gL is present [, ].
Herpesviruses are enveloped by a lipid bilayer that contains at least a dozen glycoproteins. The virion surface glycoproteins mediate recognition of susceptible cells and promote fusion of the viral envelope with the cell membrane, leading to virus entry. No single glycoprotein associated with the virion membrane has been identified as the fusogen [].Glycoprotein L (gL) forms a non-covalently linked heterodimer with glycoprotein H (gH). This heterodimer is essential for virus-cell and cell-cell fusion since the association of gH and gL is necessary for correct localisation of gH to the virion or cell surface. gH anchoring the heterodimer to the plasma membrane through its transmembrane domain. gL lacks a transmembrane domain and is secreted from cells when expressed in the absence of gH [].This entry represents Herpesvirus glycoprotein H (gH), which is a virion associated envelope glycoprotein []. Heterodimer formation between gH and gL has been demonstrated in both virions and infected cells []. Heterodimer formation between gL and gH is important for the proper folding of gH and its insertion into the membrane because the anti-gH conformation-dependent monoclonal antibodies (mAbs) 53S and LP11 bind gH only when gL is present [, ].
Herpesviruses are enveloped by a lipid bilayer that contains at least a dozen glycoproteins. The virion surface glycoproteins mediate recognition of susceptible cells and promote fusion of the viral envelope with the cell membrane, leading to virus entry. No single glycoprotein associated with the virion membrane has been identified as the fusogen [].Glycoprotein L (gL) forms a non-covalently linked heterodimer with glycoprotein H (gH). This heterodimer is essential for virus-cell and cell-cell fusion since the association of gH and gL is necessary for correct localisation of gH to the virion or cell surface. gH anchoring the heterodimer to the plasma membrane through its transmembrane domain. gL lacks a transmembrane domain and is secreted from cells when expressed in the absence of gH [].This superfamily represents a subgroup of gL found in rhadinoviruses.
Herpesviruses are enveloped by a lipid bilayer that contains at least a dozen glycoproteins. The virion surface glycoproteins mediate recognition of susceptible cells and promote fusion of the viral envelope with the cell membrane, leading to virus entry. No single glycoprotein associated with the virion membrane has been identified as the fusogen [].Glycoprotein L (gL) forms a non-covalently linked heterodimer with glycoprotein H (gH). This heterodimer is essential for virus-cell and cell-cell fusion since the association of gH and gL is necessary for correct localisation of gH to the virion or cell surface. gH anchoring the heterodimer to the plasma membrane through its transmembrane domain. gL lacks a transmembrane domain and is secreted from cells when expressed in the absence of gH [].
Herpesvirus glycoprotein H (gH) is a virion associated envelope glycoprotein []. Complex formation between gH and gL has been demonstrated in both virions and infected cells []. This entry represents the C-terminal domain.
Gamma-glutamyl hydrolase (GH) is a lysosomal and secreted glycoprotein that hydrolyses the gamma-glutamyl tail of antifolate and folate polyglutamates. Tumour cells that have high levels of GH are inherently resistant to classical antifolates, and further resistance can be acquired by elevations in GH following exposure to this class of anti-tumour agents. The highest level of expression in normal tissues occurs in the liver and kidney in humans. GH is a low-affinity (micromolar), high-turnover enzyme that has a cysteine at the active site. GH is being evaluated as an intracellular target for inhibition in order to enhance the therapeutic activity of antifolates and fluorouracil [].The 3-dimensional structure of GH shows a central eight-stranded β-sheet, which is sandwiched by three and five α-helices on each side (see []. The fold resembles that of glutamine amidotransferases (GATase) of class I, which are characterised by a conserved Cys-His-Glu active site. The major differences consist of extensions in four loops and at the C terminus of GGH. The active site residues are well conserved and the catalytically essential cysteine, positioned at a nucleophile elbow, suggests that GGH is a cysteine peptidase.
Growth hormone receptor binding protein is produced either by proteolysis of the growth hormone receptor (GHR) at the cell surface thereby releasing its extracellular domain, the GHBP (growth hormone-binding protein), or, in rodents, by alternative processing of the GHR transcript. The sheddase proteolytic enzyme responsible for the cleavage is TACE (tumour necrosis factor-alpha-converting enzyme) [, ].Growth hormone (GH) binding to GH receptor is the initial step that leads to the physiological functions of the hormone []. The biological effects of GHBP are determined by the serum levels of GH, which can vary. Low levels of GH can result in a dwarf phenotype and have been positively correlated with an increased life expectancy. High levels of GH can lead to gigantism or a clinical syndrome termed acromegaly and have been implicated in diabetic eye and kidney damage [].
Glycoprotein L from Cytomegalovirus serves a chaperone for the correct folding and surface expression of glycoprotein H (gH) []. Glycoprotein L is a member of the heterotrimeric gCIII complex of glycoproteins which also includes gH and gO and has an essential role in viral fusion [].
This entry includes envelope glycoprotein L (gL) from Herpesviruses. Glycoproteins H (gH) and L form a heterodimer which is required for the fusion of viral and plasma membranes enabling the virus to enter the host cell. In the complex, gH is inhibited until the complex binds to a host integrin and gL dissociates from the complex [].
This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria and archaea. Proteins in this family are typically between 352 and 375 amino acids in length. It contains the conserved motifs FHFxxxP, GH and PD, and a conserved Phe residue at the C-terminal.
Somatotropin, also known as growth hormone (GH), plays an important role in growth control. In addition to the growth-stimulating effect, GH is able to exert both insulin-like and insulin-antagonistic effects in adipose tissue and skeletal muscle []. The 3D structure of bovine somatotropin has been predicted using a combination of heuristics and energy minimisation [].
This is a five-bladed β-propeller fold catalytic domain where each blade has four twisted antiparallel β-strands radially orientated around a pseudo-5-fold axis []. It can be found in the glycosyl hydrolase family 43 (GH43) members, including beta-xylosidases, alpha-L-arabinanases and bifunctional beta-xylosidases/alpha-L-arabinofuranosidases [, , ]. This domain can also be found in other GH families, such as GH32, GH62 and GH68 [].
Growth hormone (GH) is a pituitary hormone involved in cell and overall bodygrowth, carbohydrate-protein-lipid metabolism and osmotic homeostasis.Control of GH release was initially ascribed to 2 pathways: stimulation byhypothalamic GH-releasing hormone (GHRH) and inhibition by somatostatin.More recently, synthetic compounds, termed GH secretagogues (GHS), were shown to stimulate GH release strongly. This effect is elicited by an orphanG protein-coupled receptor (GPCR), subsequently named the GHS receptor(GHS-R). The endogenous ligand for this receptor was purified from rat andhuman stomach and named ghrelin [].The purified cDNA for ghrelin encodes a 117 amino acid prepropeptide. Thefirst 23 amino acid residues form a signal peptide that is cleaved to leaveproghrelin. Residues 24-51 are cleaved to yield active ghrelin, discardingthe C-terminal fragment []. The 28-residue ghrelin peptide that is left is biologically inactive. Esterification with n-octanoic acid at Ser3 is required for biological activity. Ghrelin mRNA is expressed mainly in thestomach in a distinct endocrine cell type in the submucosal layer, known asX/A-like cells. The active peptide is secreted into the bloodstream ratherthan the stomach. Ghrelin responsive cells are found in abundance in a limited area of the hypothalamic arcuate nucleus (ARC), a region involved incontrol of food intake. As well as releasing GH indirectly via its action on the ARC region of the hypothalamus, ghrelin also appears to be able tostimulate GH release via direct action on the pituitary [].A further variant of the ghrelin peptide exists in rat stomach, des-Gln14-ghrelin. This is produced by alternative splicing and does not require theesterification by n-octanoic acid for biological activity. However, its presence in only small quantities in the stomach suggests ghrelin is themajor active form. The ghrelin active peptide and the GHS receptor sharesequence similarity with motilin and the motilin receptor, respectively, suggesting an evolutionary relationship.
This entry represents a family of glycosyl hydrolases (GH) from CAZy family 18 that are mainly found in Bacteroidetes, including the endoglycosidase BT1044 from Bacteroides thetaiotaomicron (). This protein folds into the canonical (β/α)8 barrel (TIM barrel) fold common to many GH structures, with the N-terminal a discrete extended structure that would orientate the lipoprotein on the cell surface with the active site facing the extracellular environment [].
Herpesvirus glycoprotein H (gH) is a virion associated envelope glycoprotein []. Complex formation between gH and gL has been demonstrated in both virions and infected cells []. This superfamily represents the C-terminal domain.Structurally, the C-terminal domain consists of 8 beta sheets and 1 small alpha helix. The beta sheets are arranged into a beta sandwich, made up of two apposed beta sheets, each made up of four strands. Within Herpesvirus glycoprotein H, the two sheets are termed the N sheet and C sheet, since they are sequential. The alpha helix sits in the loop between two of the beta strands, and packs against the C sheet.
This family includes both FMRFamide-related peptides andgrowth hormone-releasing peptides.FMRFamide-related peptides are neurotransmitters, hormone-like substances and tumor suppressor peptides []. Neuropeptide RFRP-1 acts as a potent negative regulator of gonadotropin synthesis and secretion. Neuropeptides NPSF and NPVF efficiently inhibit forskolin-induced production of cAMP, but RFRP-2 shows no inhibitory activity. Neuropeptide NPVF blocks morphine-induced analgesia. FMRFamide-related peptides may act in concert with kisspeptin, through opposing affects, to regulate the activity of gonadotropin-releasing hormone (GnRH) neurons across the seasons, leading to an annual change in fertility and the cyclical seasonal transition from non-breeding to breeding season [, , ]. The primary role of growth hormone-releasing peptide (fGRP) is to release GH from the pituitary [].
This entry represents a domain found in the glycosyl hydrolase family 26 members. Glycoside hydrolases (GHs) play a critical role in both eukaryotes andprokaryotes, where they fulfill numerous important functions such as substrateacquisition and the remote remodelling of cell walls and the glycandecorations of glycoproteins. GH family 26 consists mainly of endo-beta-1,4-mannanases (mannanases) (), although some members of this family display beta-1,3-xylanase activity. Proteins containing this domain also include the enzyme endogluconase H (), which catalyses the endohydrolysis of 1,4-beta-glucosidic linkages in cellulose, lichenin and cereal beta-D-glucans. The family 26 GHs are members of clan GH-A[, , , ].The GH26 catalytic domain exhibits the architecture of the classical(beta/alpha)8-barrel folding motif characteristic of a clan-GH-A member. Two Glu residues located respectively on strands beta-4 andbeta-7 act as the catalytic acid/base and nucleophile in a double-displacementmechanism [, , ].
Somatostatin (SST), also known as somatotropin release-inhibiting factor (SRIF), is a hypothalamic hormone, a pancreatic hormone, and a central and peripheral neurotransmitter. Somatostatin has a wide distribution throughout the central nervous system (CNS) as well as in peripheral tissues, for example in the pituitary, pancreas and stomach. The various actions of somatostatin are mediated by a family of rhodopsin-like G protein-coupled receptors, which comprise of five distinct subtypes: Somatostatin receptor 1 (SSTR1), Somatostatin receptor 2 (SSTR2), Somatostatin receptor 3 (SSTR3), Somatostatin receptor 4 (SSTR4) and Somatostatin receptor 5 (SSTR5) [, , ]. These subtypes are widely expressed in many tissues [, , , , , ], and frequently multiple subtypes coexist in the same cell []. The somatostatin receptor subtypes also share common signalling pathways, such as the inhibition of adenylyl cyclase [, ], activation of phosphotyrosine phosphatase (PTP), and modulation of mitogen-activated protein kinase (MAPK) through G protein-dependent mechanisms. Some of the subtypes are also coupled to inward rectifying K+ channels (SSTR2, SSTR3, SSTR4, SSTR5) [, ], to voltage-dependent Ca2+ channels (SSTR1, SSTR2) [], to an Na+/H+ exchanger (SSTR1), AMPA/kainate glutamate channels (SSTR1, SSTR2), phospholipase C (SSTR2, SSTR5), and phospholipase A2 (SSTR4) []. Amongst the wide spectrum of somatostatin effects, several biological responses have been identified that display absolute or relative subtype selectivity. These include GH secretion (SSTR2 and 5), insulin secretion (SSTR5), glucagon secretion (SSTR2), and immune responses (SSTR2) [].This entry represents the somatostatin family.
G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups []. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence []. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [, , , , ]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice []. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [].The secretin-like GPCRs include secretin [], calcitonin [], parathyroid hormone/parathyroid hormone-related peptides []and vasoactive intestinal peptide [], all of which activate adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. These receptors contain seven transmembrane regions, in a manner reminiscent of the rhodopsins and other receptors believed to interact with G-proteins (however there is no significant sequence identity between these families, the secretin-like receptors thus bear their own unique '7TM' signature). Their N-terminal is probably located on the extracellular side of the membrane and potentially glycosylated. This N-terminal region contains a long conserved region which allows the binding of large peptidic ligand such as glucagon, secretin, VIP and PACAP; this region contains five conserved cysteines residues which could be involved in disulphide bond. The C-terminal region of these receptor is probably cytoplasmic. Every receptor gene in this family is encoded on multiple exons, and several of these genes are alternatively spliced to yield functionally distinct products. Growth hormone (GH)-releasing hormone (GHRH) belongs to the family of gut-neuropeptide hormones that includes glucagon, secretin and vasoactive intestinal peptide (VIP) []. The receptors for this peptide family involve similar signal transduction pathways - on hormone binding, they interact with G protein and cause stimulation of adenylate cyclase []. Acting through the GHRH receptor (GHRHR), GH plays a pivotal role in the regulation of GH synthesis and secretion in the pituitary, possibly serving other roles in different tissues []. Cryo-electron microscopy shows a hormone recognition pattern where an α-helical GHRH forms interactions involving all the extracellular loops, most TM helices, and a linker from GHRHR []. The human pituitary GHRHR is a 423-amino acid protein that has the characteristic 7TM signature of the secretin-like GPCR superfamily, sharing 47%, 42%, 35%, and 28% identity with receptors for VIP, secretin, calcitonin and PTH, respectively [].
Somatostatin (SST), also known as somatotropin release-inhibiting factor (SRIF), is a hypothalamic hormone, a pancreatic hormone, and a central and peripheral neurotransmitter. Somatostatin has a wide distribution throughout the central nervous system (CNS) as well as in peripheral tissues, for example in the pituitary, pancreas and stomach. The various actions of somatostatin are mediated by a family of rhodopsin-like G protein-coupled receptors, which comprise of five distinct subtypes: Somatostatin receptor 1 (SSTR1), Somatostatin receptor 2 (SSTR2), Somatostatin receptor 3 (SSTR3), Somatostatin receptor 4 (SSTR4) and Somatostatin receptor 5 (SSTR5) [, , ]. These subtypes are widely expressed in many tissues [, , , , , ], and frequently multiple subtypes coexist in the same cell []. The somatostatin receptor subtypes also share common signalling pathways, such as the inhibition of adenylyl cyclase [, ], activation of phosphotyrosine phosphatase (PTP), and modulation of mitogen-activated protein kinase (MAPK) through G protein-dependent mechanisms. Some of the subtypes are also coupled to inward rectifying K+ channels (SSTR2, SSTR3, SSTR4, SSTR5) [, ], to voltage-dependent Ca2+ channels (SSTR1, SSTR2) [], to an Na+/H+ exchanger (SSTR1), AMPA/kainate glutamate channels (SSTR1, SSTR2), phospholipase C (SSTR2, SSTR5), and phospholipase A2 (SSTR4) []. Amongst the wide spectrum of somatostatin effects, several biological responses have been identified that display absolute or relative subtype selectivity. These include GH secretion (SSTR2 and 5), insulin secretion (SSTR5), glucagon secretion (SSTR2), and immune responses (SSTR2) [].This entry represents SSTR2. In humans has been found in high levels the brain, kidney and pituitary, with lower levels in the jejunum, pancreas, colon and liver. All five human somatostatin receptors expressed in COS-7 cells are coupled to activation of phosphoinositide (PI)-specific PLC-beta; and Ca2+ mobilisation via pertussis toxin-sensitive G protein(s) with an order of potency of SSTR5 >SSTR2 >SSTR3 >SSTR4 >SSTR1 [].
Somatostatin (SST), also known as somatotropin release-inhibiting factor (SRIF), is a hypothalamic hormone, a pancreatic hormone, and a central and peripheral neurotransmitter. Somatostatin has a wide distribution throughout the central nervous system (CNS) as well as in peripheral tissues, for example in the pituitary, pancreas and stomach. The various actions of somatostatin are mediated by a family of rhodopsin-like G protein-coupled receptors, which comprise of five distinct subtypes: Somatostatin receptor 1 (SSTR1), Somatostatin receptor 2 (SSTR2), Somatostatin receptor 3 (SSTR3), Somatostatin receptor 4 (SSTR4) and Somatostatin receptor 5 (SSTR5) [, , ]. These subtypes are widely expressed in many tissues [, , , , , ], and frequently multiple subtypes coexist in the same cell []. The somatostatin receptor subtypes also share common signalling pathways, such as the inhibition of adenylyl cyclase [, ], activation of phosphotyrosine phosphatase (PTP), and modulation of mitogen-activated protein kinase (MAPK) through G protein-dependent mechanisms. Some of the subtypes are also coupled to inward rectifying K+ channels (SSTR2, SSTR3, SSTR4, SSTR5) [, ], to voltage-dependent Ca2+ channels (SSTR1, SSTR2) [], to an Na+/H+ exchanger (SSTR1), AMPA/kainate glutamate channels (SSTR1, SSTR2), phospholipase C (SSTR2, SSTR5), and phospholipase A2 (SSTR4) []. Amongst the wide spectrum of somatostatin effects, several biological responses have been identified that display absolute or relative subtype selectivity. These include GH secretion (SSTR2 and 5), insulin secretion (SSTR5), glucagon secretion (SSTR2), and immune responses (SSTR2) [].This entry represents SSTR1 []. In humans, it is expressed at high levels in the jejunum and stomach, with lower levels in the pancreas, colon and kidney, but it is absent in the brain. Conversely, in rodent tissue, high levels are found in the brain, but are absent in peripheral tissues []. All five human somatostatin receptors expressed in COS-7 cells are coupled to activation of phosphoinositide (PI)-specific PLC-beta; and Ca2+ mobilisation via pertussis toxin-sensitive G protein(s) with an order of potency of SSTR5 >SSTR2 >SSTR3 >SSTR4 >SSTR1 [].
Somatostatin (SST), also known as somatotropin release-inhibiting factor (SRIF), is a hypothalamic hormone, a pancreatic hormone, and a central and peripheral neurotransmitter. Somatostatin has a wide distribution throughout the central nervous system (CNS) as well as in peripheral tissues, for example in the pituitary, pancreas and stomach. The various actions of somatostatin are mediated by a family of rhodopsin-like G protein-coupled receptors, which comprise of five distinct subtypes: Somatostatin receptor 1 (SSTR1), Somatostatin receptor 2 (SSTR2), Somatostatin receptor 3 (SSTR3), Somatostatin receptor 4 (SSTR4) and Somatostatin receptor 5 (SSTR5) [, , ]. These subtypes are widely expressed in many tissues [, , , , , ], and frequently multiple subtypes coexist in the same cell []. The somatostatin receptor subtypes also share common signalling pathways, such as the inhibition of adenylyl cyclase [, ], activation of phosphotyrosine phosphatase (PTP), and modulation of mitogen-activated protein kinase (MAPK) through G protein-dependent mechanisms. Some of the subtypes are also coupled to inward rectifying K+ channels (SSTR2, SSTR3, SSTR4, SSTR5) [, ], to voltage-dependent Ca2+ channels (SSTR1, SSTR2) [], to an Na+/H+ exchanger (SSTR1), AMPA/kainate glutamate channels (SSTR1, SSTR2), phospholipase C (SSTR2, SSTR5), and phospholipase A2 (SSTR4) []. Amongst the wide spectrum of somatostatin effects, several biological responses have been identified that display absolute or relative subtype selectivity. These include GH secretion (SSTR2 and 5), insulin secretion (SSTR5), glucagon secretion (SSTR2), and immune responses (SSTR2) [].This entry represents SST5R. It is expressed in range of tissues including the small intestine, heart, adrenal, cerebellum, pituitary, placenta and skeletal muscle. It is also expressed in pancreatic islets [], where somatostatin is a known regulator of insulin and glucagon secretion. All five human somatostatin receptors expressed in COS-7 cells have been shown to couple to activation of phosphoinositide (PI)-specific PLC-beta; and Ca2+ mobilisation via pertussis toxin-sensitive G protein(s) with an order of potency of SSTR5 >SSTR2 >SSTR3 >SSTR4 >SSTR1 [].
Somatostatin (SST), also known as somatotropin release-inhibiting factor (SRIF), is a hypothalamic hormone, a pancreatic hormone, and a central and peripheral neurotransmitter. Somatostatin has a wide distribution throughout the central nervous system (CNS) as well as in peripheral tissues, for example in the pituitary, pancreas and stomach. The various actions of somatostatin are mediated by a family of rhodopsin-like G protein-coupled receptors, which comprise of five distinct subtypes: Somatostatin receptor 1 (SSTR1), Somatostatin receptor 2 (SSTR2), Somatostatin receptor 3 (SSTR3), Somatostatin receptor 4 (SSTR4) and Somatostatin receptor 5 (SSTR5) [, , ]. These subtypes are widely expressed in many tissues [, , , , , ], and frequently multiple subtypes coexist in the same cell []. The somatostatin receptor subtypes also share common signalling pathways, such as the inhibition of adenylyl cyclase [, ], activation of phosphotyrosine phosphatase (PTP), and modulation of mitogen-activated protein kinase (MAPK) through G protein-dependent mechanisms. Some of the subtypes are also coupled to inward rectifying K+ channels (SSTR2, SSTR3, SSTR4, SSTR5) [, ], to voltage-dependent Ca2+ channels (SSTR1, SSTR2) [], to an Na+/H+ exchanger (SSTR1), AMPA/kainate glutamate channels (SSTR1, SSTR2), phospholipase C (SSTR2, SSTR5), and phospholipase A2 (SSTR4) []. Amongst the wide spectrum of somatostatin effects, several biological responses have been identified that display absolute or relative subtype selectivity. These include GH secretion (SSTR2and 5), insulin secretion (SSTR5), glucagon secretion (SSTR2), and immune responses (SSTR2) [].This entry represents SSTR4. It is present in high levels in the pituitary, but is less abundant in the brain and peripheral tissues [, , ]. All five human somatostatin receptors expressed in COS-7 cells are coupled to activation of phosphoinositide (PI)-specific PLC-beta; and Ca2+ mobilisation via pertussis toxin-sensitive G protein(s) with an order of potency of SSTR5 >SSTR2 >SSTR3 >SSTR4 >SSTR1 [].
Somatostatin (SST), also known as somatotropin release-inhibiting factor (SRIF), is a hypothalamic hormone, a pancreatic hormone, and a central and peripheral neurotransmitter. Somatostatin has a wide distribution throughout the central nervous system (CNS) as well as in peripheral tissues, for example in the pituitary, pancreas and stomach. The various actions of somatostatin are mediated by a family of rhodopsin-like G protein-coupled receptors, which comprise of five distinct subtypes: Somatostatin receptor 1 (SSTR1), Somatostatin receptor 2 (SSTR2), Somatostatin receptor 3 (SSTR3), Somatostatin receptor 4 (SSTR4) and Somatostatin receptor 5 (SSTR5) [, , ]. These subtypes are widely expressed in many tissues [, , , , , ], and frequently multiple subtypes coexist in the same cell []. The somatostatin receptor subtypes also share common signalling pathways, such as the inhibition of adenylyl cyclase [, ], activation of phosphotyrosine phosphatase (PTP), and modulation of mitogen-activated protein kinase (MAPK) through G protein-dependent mechanisms. Some of the subtypes are also coupled to inward rectifying K+ channels (SSTR2, SSTR3, SSTR4, SSTR5) [, ], to voltage-dependent Ca2+ channels (SSTR1, SSTR2) [], to an Na+/H+ exchanger (SSTR1), AMPA/kainate glutamate channels (SSTR1, SSTR2), phospholipase C (SSTR2, SSTR5), and phospholipase A2 (SSTR4) []. Amongst the wide spectrum of somatostatin effects, several biological responses have been identified that display absolute or relative subtype selectivity. These include GH secretion (SSTR2 and 5), insulin secretion (SSTR5), glucagon secretion (SSTR2), and immune responses (SSTR2) [].This entry represents SSTR3. It is widely distributed in mouse brain, with high levels in the forebrain, hippocampus and amygdala; moderate levels are also present in the substantia nigra. All five human somatostatin receptors expressed in COS-7 cells are coupled to activation of phosphoinositide (PI)-specific PLC-beta; and Ca2+ mobilisation via pertussis toxin-sensitive G protein(s) with an order of potency of SSTR5 >SSTR2 >SSTR3 >SSTR4 >SSTR1 []. Inhibition of angiogenesis has been shown to be via the SSTR3, and involves the inhibition of MAPK and endothelial nitric oxide synthase (eNOS) activity [].
