We found a significant increase in the Gbeta3 T allele (OR ......
We found a significant increase in the Gbeta3 T allele (OR = 1.61, 95% CI 1.17-2.2, P = 0.0035) and a marginal altered genotype distribution of the ACE ID polymorphism with decrease in the II genotypes (chi(2) = 6.43, df=3, P = 0.04) in the patients' group. Analysing the data for both genes we found that the combined actions of ACE and Gbeta3 genotypes accumulate in carriers of the ACE D allele (ID and DD) and Gbeta3 TT homozygotes with ID/DD-TT carriers showing a more than five-fold increase in risk for major depression (crude OR = 5.83, 95% CI 1.99-17.08, P = 0.0002).More...
Positive relationships between GNB3 and other components at different levels (count: 1)
Genetic/epigenetic locus
Protein and other molecule
Cell and molecular pathway
Neural system
Cognition and behavior
Symptoms and signs
Environment
Positive relationship network of GNB3 in MK4MDD
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Note:
1. The different color of the nodes denotes the level of the nodes.
Genetic/Epigenetic Locus
Protein and Other Molecule
Cell and Molecular Pathway
Neural System
Cognition and Behavior
Symptoms and Signs
Environment
MDD
2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network.
If the mapped gene or protein is not from literature, square node would be used instead of Circle node.
Accordingly, the relationship is marked with dot line.
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3. The network is generated using Cytoscape Web
Negative relationships between GNB3 and MDD (count: 0)
Negative relationships between GNB3 and other components at different levels (count: 0)
Inflammatory immune response requires the recruitment of leu......
Inflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for the cell trafficking and thus are vital for protective host response. In addition, chemokines regulate plethora of biological processes of hematopoietic cells to lead cellular activation, differentiation and survival. The chemokine signal is transduced by chemokine receptors (G-protein coupled receptors) expressed on the immune cells. After receptor activation, the alpha- and beta-gamma-subunits of G protein dissociate to activate diverse downstream pathways resulting in cellular polarization and actin reorganization. Various members of small GTPases are involved in this process. Induction of nitric oxide and production of reactive oxygen species are as well regulated by chemokine signal via calcium mobilization and diacylglycerol production.More...
All taste pathways are proposed to converge on common elemen......
All taste pathways are proposed to converge on common elements that mediate a rise in intracellular Ca2+ followed by neurotransmitter release. Na+ salt depolarizes taste cells by passive influx of Na+ through the amiloride-sensitive Na+ channel (ENaC). Acids depolarize taste cells by a variety of mechanisms, including influx of protons (H+) through ENaC and a proton-gated cation channel (MDEG). Two putative umami receptors have been identified: a truncated variant of the metabotropic glutamate receptor mGluR4 and the heterodimer, T1R1 + T1R3. Umami receptors are coupled to a signaling pathway involving activation of PLCbeta2, production of IP3 and diacylglycerol, release of Ca2+ from intracellular stores and activation of a transient receptor potential channel, TRPM5. Bitter compounds, such as denatonium and PROP, activate particular T2R/TRB isoforms, which activate gustducin heterotrimers. Activated alpha-gustducin stimulates PDE to hydrolyze cAMP, whereas betagamma subunits activate PLCbeta2 to generate IP3, which leads to release of Ca2+ from internal stores. Artificial sweeteners activate GPCRs (T1R heterodimers) apparently linked via PLC to IP3 production and release of Ca2+ from intracellular stores. Sugars apparently activate GPCRs linked via AC to cAMP production which, in turn, may inhibit basolateral K+ channels through phosphorylation by cAMP-activated protein kinase A (PKA).More...
The classic signalling route for G alpha (q) is activation o......
The classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides a path to calcium-regulated kinases and phosphatases, GEFs, MAP kinase cassettes and other proteins that mediate cellular responses ranging from granule secretion, integrin activation, and aggregation in platelets. Gq participates in many other signalling events including direct interaction with RhoGEFs that stimulate RhoA activity and inhibition of PI3K. Both in vitro and in vivo, the G-protein Gq seems to be the predominant mediator of the activation of platelets.More...
Hemostasis is a physiological response that culminates in th......
Hemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Acute vessel injury results in its constriction to reduce the loss of blood. Under normal conditions vascular endothelium supports vasodilation, inhibits platelet adhesion and activation, suppresses coagulation, enhances fibrin cleavage and is anti-inflammatory in character. Under acute vascular trauma vasoconstrictor mechanisms predominate and the endothelium becomes prothrombotic, procoagulatory and proinflammatory in nature. This is achieved by a reduction of endothelial dilating agents: adenosine, NO and prostacyclin; and the direct action of ADP, serotonin and thromboxane on vascular smooth muscle cells to elicit their contraction. The chief trigger for the change in endothelial function that leads to the formation of haemostatic thrombus is the loss of the endothelial cell barrier between blood and ECM components. Circulating platelets identify and discriminate areas of endothelial lesions; here, they adhere to the exposed sub endothelium. Their interaction with the various thrombogenic substrates and locally generated or released agonists results in platelet activation. This process is described as possessing two stages, firstly, adhesion - the initial tethering to a surface, and secondly aggregation - the platelet-platelet cohesion.More...
Thromboxane (TXA2) binds to the thromboxane receptor (TP). T......
Thromboxane (TXA2) binds to the thromboxane receptor (TP). There are 2 splice variant forms of TP, differing in their cytoplasmic carboxyl terminal tails. TP beta was first identified in endothelial cells. TP alpha was identified in platelets and placenta. The major signalling route for TP is Gq-mediated stimulation of PLC and consequent increase in cellular calcium. TP also couples to G13, leading to stimulation of Rho and Rac.More...
Platelet activation begins with the initial binding of adhes......
Platelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists. Intracellular signaling reactions will then enhance the adhesive and procoagulant properties of tethered platelets or of platelets circulating in the proximity. From the subendothelial adhesive substrates, collagen and possibly vWF are the main inducers of platelet activation. GP VI is the most potent collagen receptor initiating signal generation, an ability derived from its interaction with the FcRI gamma chain. This results in the phosphorylation of the gamma-chain by the non-receptor tyrosine kinases of the Src family. The phosphotyrosine motif is recognized by the SH2 domains of Syk, a tyrosine kinase. This association activates the Syk enzyme, leading to activation. Four PARs are identified, of which PARs 1 ,3 and 4 are substrates for thrombin. PAR 1 is the predominant thrombin receptor, PAR 3 is minimally expressed and PAR 4 is less responsive to thrombin. Platelets do not store PAR1, due to limited protein synthesis, they are capable of responding to thrombin only once. Platelet activation further results in the scramblase-mediated transport of negatively-charged phospholipids to the platelet surface. These phospholipids provide a catalytic surface (with the charge provided by phosphatidylserine and phosphatidylethanolamine) for the tenase complex (formed by the activated forms of the blood coagulation factors factor VIII and factor I).More...
Two principal mechanisms limit blood loss after vascular inj......
Two principal mechanisms limit blood loss after vascular injury. Initially, platelets are activated, adhere to the site of the injury, and aggregate into a plug that limits blood loss. Proteins and small molecules released from activated platelets stimulate the plug formation process, and fibrinogen from the plasma forms bridges between activated platelets. These events allow the initiation of the clotting cascade, the second mechanism to limit blood loss. Negatively charged phospholipids exposed on cell surfaces at the site of injury and on activated platelets interact with tissue factor, setting off a cascade of reactions leading to generation of fibrin and the formation of an insoluble fibrin clot that strengthens the platelet plug.More...
In the initial response to injury, platelets adhere to damag......
In the initial response to injury, platelets adhere to damaged blood vessels, responding to the exposure of collagen from the vascular epithelium. Once adhered they degranulate, releasing agents such as serotonin and ADP and synthesize Thromboxane A2, all of which amplify the response, recruiting further platelets to the area and promoting platelet aggregation.More...
The neurotransmitter in the synaptic cleft released by the p......
The neurotransmitter in the synaptic cleft released by the pre-synaptic neuron binds specific receptors located on the post-synaptic terminal. These receptors are either ion channels or G protein coupled receptors that function to transmit the signals from the post-synaptic membrane to the cell body.More...
Glucagon and insulin are peptide hormones released from the ......
Glucagon and insulin are peptide hormones released from the pancreas into the blood, that normally act in complementary fashion to stabilize blood glucose concentration. When blood glucose levels rise, insulin release stimulates glucose uptake from the blood, glucose breakdown.More...
Phospholipase C beta (PLCbeta) isoforms are activated by G-p......
Phospholipase C beta (PLCbeta) isoforms are activated by G-protein beta:gamma in the order PLCB3 > PLCB2 > PLCB1. Gbeta:gamma binds to the pleckstrin homology domain of PLC beta, increasing phospholipase activity and leading to increased hydrolysis of PIP2 to DAG and IP3.More...
Guanine nucleotide binding proteins or G proteins constitute......
Guanine nucleotide binding proteins or G proteins constitute a large family of proteins that transmit signals from membrane receptors to downstream effector molecules. Each G protein is composed of 3 subunits: alpha, beta and gamma. The alpha subunit binds to guanine nucleotide and is important for receptor coupling and effector activation. Each of s, i and q - forms of the alpha subunit has a functional specificity. About 4 isoforms of the beta subunit are known. Of the 12 subunits of gamma subunits known so far, subunits 1 and 9 are active in photoreceptor coupled signalling while others are expressed in various tissues. The beta and gamma subunits occur as dimers on the cell surface and the specific role, tissue occurrence and the binding preferences between isoforms of these subunits are still being unraveled.More...
G protein-coupled receptors. The beta:gamma G-protein dimer ......
G protein-coupled receptors. The beta:gamma G-protein dimer is also involved in downstream signaling , and some receptors form part of metastable complexes of receptor and accessory proteins such as the arrestins. GPCRs are involved in many diverse signaling events , using a variety of pathways that include modulation of adenylyl cyclase, phospholipase C, the mitogen activated protein kinases (MAPKs), extracellular signal regulated kinase (ERK) c-Jun-NH2-terminal kinase (JNK) and p38 MAPK.More...
Chemical synapses are specialized junctions that are used fo......
Chemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron, muscle cell or glad cell. The pre and the post-synaptic cell are separated by a gap of 20nm called the synaptic cleft. The signals pass in a unidirection from pre-synaptic to post-synaptic. The pre-synaptic neuron communicates via the release of neurotransmitter which bind the receptors on the post-synaptic cell.More...
PI3K gamma (PI3KG) is a heterodimer consisting of a p110 cat......
PI3K gamma (PI3KG) is a heterodimer consisting of a p110 catalytic subunit associated with a regulatory p101 or p84 subunit. PI3KG is most highly expressed in neutrophils, where the p101 form predominates (approximately 95%). G beta:gamma recruits PI3KG to the plasma membrane, both activating PI3KG and providing access to its substrate PIP2, which is converted to PIP3.More...
Glucagon-like Peptide-1 (GLP-1) is secreted by L-cells in th......
Glucagon-like Peptide-1 (GLP-1) is secreted by L-cells in the intestine in response to glucose and fatty acids. GLP-1 circulates to the beta cells of the pancreas where it binds a G-protein coupled receptor, GLP-1R, on the plasma membrane. The binding activates the heterotrimeric G-protein G(s), causing the alpha subunit of G(s) to exchange GDP for GTP and dissociate from the beta and gamma subunits. The activated G(s) alpha subunit interacts with Adenylyl Cyclase VIII (Adenylate Cyclase VIII, AC VIII) and activates AC VIII to produce cyclic AMP (cAMP). cAMP then has two effects: 1) cAMP activates Protein Kinase A (PKA), and 2) cAMP activates Epac1 and Epac2, two guanyl nucleotide exchange factors. Binding of cAMP to PKA causes the catalytic subunits of PKA to dissociate from the regulatory subunits and become an active kinase. PKA is known to enhance insulin secretion by closing ATP-sensitive potassium channels, closing voltage-gated potassium channels, releasing calcium from the endoplasmic reticulum, and affecting insulin secretory granules. The exact mechanisms for PKA's action are not fully known. After prolonged increases in cAMP, PKA translocates to the nucleus where it regulates the PDX-1 and CREB transcription factors, activating transcription of the insulin gene. cAMP produced by AC VIII also activates Epac1 and Epac2, which catalyze the exchange of GTP for GDP on G-proteins, notably Rap1A.. Rap1A regulates insulin secretory granules and is believed to activate the Raf/MEK/ERK mitogenic pathway leading to proliferation of beta cells. The Epac proteins also interact with RYR calcium channels on the endoplasmic reticulum, the SUR1 subunits of ATP-sensitive potassium channels, and the Piccolo:Rim2 calcium sensor at the plasma membrane.More...
The catecholamines adrenaline (epinephrine) and noradrenalin......
The catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine) inhibit insulin secretion from pancreatic beta cells. Four effects are seen in the cells: 1. Inhibition of exocytosis of secretory granules, the major effect. 2. Opening of ATP-sensitive potassium channels (KATP channels) and repolarization of the cell. 3. Closing of L-type voltage-dependent calcium channels and inhibition of calcium influx. 4. Inhibition of adenylyl cyclase activity. The first event in adrenaline/noradrenaline signaling in beta cells is the binding of adrenaline or noradrenaline to alpha-2 adrenergic receptors, which are G-protein coupled receptors. Binding activates the alpha subunits in heterotrimeric Gi and Go complexes to exchange GDP for GTP, forming the active G alpha:GTP complex. Experiments using specific antibodies against the alpha subunits in mice show that Gi alpha-1, Gi alpha-2, and Go alpha-2 are responsible for adrenergic effects. The exact beta and gamma subunits of the heterotrimeric G-proteins are unknown. After activation by GTP, the heterotrimeric complex dissociates into the G alpha:GTP complex and the beta:gamma complex. The G alpha:GTP complex causes the inhibition of exocytosis by an unknown mechanism that involves protein acylation. This is responsible for most of the observed inhibition of insulin secretion. Additionally, the G alpha:GTP complex activates (opens) KATP channels, allowing the cell to repolarize. The beta:gamma complex inhibits (closes) voltage-dependent calcium channels, reducing the intracellular calcium concentration, and inhibits adenylyl cyclase, reducing the intracellular cAMP concentration.More...
Pancreatic beta cells integrate signals from several metabol......
Pancreatic beta cells integrate signals from several metabolites and hormones to control the secretion of insulin. In general, glucose triggers insulin secretion while other factors can amplify or inhibit the amount of insulin secreted in response to glucose. Factors which increase insulin secretion include the incretin hormones Glucose-dependent insulinotropic polypeptide (GIP and glucagon-like peptide-1 (GLP-1), acetylcholine, and fatty acids. Factors which inhibit insulin secretion include adrenaline and noradrenaline.More...
The general function of the G alpha (s) subunit (Gs) is to a......
The general function of the G alpha (s) subunit (Gs) is to activate adenylate cyclase, which in turn produces cAMP, leading to the activation of cAMP-dependent protein kinases (often referred to collectively as Protein Kinase A). The signal from the ligand-stimulated GPCR is amplified because the receptor can activate several Gs heterotrimers before it is inactivated.More...
The glucagon hormone family regulates the activity of GPCRs ......
The glucagon hormone family regulates the activity of GPCRs from the secretin receptor subfamily in Class II/B.More...
Many hormones that affect individual physiological processes......
Many hormones that affect individual physiological processes including the regulation of appetite, absorption, transport, and oxidation of foodstuffs influence energy metabolism pathways. While insulin mediates the storage of excess nutrients, glucagon is involved in the mobilization of energy resources in response to low blood glucose levels, principally by stimulating hepatic glucose output. Small doses of glucagon are sufficient to induce significant glucose elevations. These hormone-driven regulatory pathways enable the body to sense and respond to changed amounts of nutrients in the blood and demands for energy. Glucagon and Insulin act through various metabolites and enzymes that target specific steps in metabolic pathways for sugar and fatty acids. The processes responsible for the long-term control of fat synthesis and short term control of glycolysis by key metabolic products and enzymes are annotated in this module as six specific pathways: Pathway 1. Glucagon signalling in metabolic pathways: In response to low blood glucose, pancreatic alpha-cells release glucagon. The binding of glucagon to its receptor results in increased cAMP synthesis, and Protein Kinase A - Copyright National Academy of Sciences, U.S.A.).More...
Opioids are chemical substances similar to opiates, the acti......
Opioids are chemical substances similar to opiates, the active substances found in opium (morphine, codeine etc.). Opioid action is mediated by the receptors for endogenous opioids; peptides such as the enkephalins, the endorphins or the dynorphins. Opioids possess powerful analgesic and sedative effects, and are widely used as pain-killers. Their main side-effect is the rapid establishment of a strong addiction. Opioids receptors are G-protein coupled receptors (GPCR). There are four classes of receptors: mu (MOR), kappa (KOR) and delta (DOR), and the nociceptin receptor (NOP).More...
Receptor activated heterotrimeric G proteins consist of the ......
Receptor activated heterotrimeric G proteins consist of the Galpha and the tightly associated Gbeta-gamma subunits. When a ligand binds to a G protein-coupled receptor, it stabilises a conformation with an high affinity for the G-protein bound to GDP. GDP is then exchanged for GTP on the Galpha subunit. This exchange triggers the dissociation of the Galpha subunit from the Gbeta-gamma dimer and the receptor. Galpha-GTP and Gbeta-gamma, can then modulate different signalling cascades and effector proteins, while the receptor is able to activate another G protein, resulting in an amplification cascade. The Galpha subunit will eventually hydrolyze the attached GTP to GDP by its inherent enzymatic activity, allowing it to reassociate with Gbeta-gamma and start a new cycle.More...
The classical role of the G-protein beta/gamma dimer was bel......
The classical role of the G-protein beta/gamma dimer was believed to be the inactivation of the alpha subunit, Gbeta/gamma was viewed as a negative regulator of Galpha signalling. It is now known that Gbeta/gamma subunits can directly modulate many effectors, including some also regulated by G alpha.More...
There are more than 800 G-protein coupled receptor. GPCRs ar......
There are more than 800 G-protein coupled receptor. GPCRs are receptors for a diverse range of ligands from large proteins to photons and have an equal diverstiy of ligand-binding mechanisms. Classical GPCR signaling involves signal transduction via heterotrimeric G-proteins, however many G-protein independent mechanisms have been reported.More...
Kainate receptors are found both in the presynaptc terminals......
Kainate receptors are found both in the presynaptc terminals and the postsynaptic neurons. Kainate receptor activation could lead to either ionotropic activity (influx of Ca2+ or Na+ and K+) in the postsynaptic neuron or coupling of the receptor with G proteins in the presynaptic and the postsynaptic neurons. Kainate receptors are tetramers made from subunits GRIK1-5 or GluR5-7 and KA1-2. Activation of kainate receptors made from GRIK1 or KA2 release Ca2+ from the intracellular stores in a G protein-dependent manner. The G protein involved in this process is sensitive to pertussis toxin.More...
Thrombin activates proteinase activated receptors (PARs) tha......
Thrombin activates proteinase activated receptors (PARs) that signal through heterotrimeric G proteins of the G12/13 and Gq families, thereby connecting to a host of intracellular signaling pathways. Thrombin activates PARs by cleaving an N-terminal peptide that then binds to the body of the receptor to effect transmembrane signaling. Intermolecular ligation of one PAR molecule by another can occur but is less efficient than self-ligation. A synthetic peptide of sequence SFLLRN, the first six amino acids of the new N-terminus generated when thrombin cleaves PAR1, can activate PAR1 independent of protease and receptor cleavage. PARs are key to platelet activation; PAR1 and PAR4 are the predominant PARs expressed in platelets, the role of PAR3 is doubtful, PAR2 is not expressed in platelets. In mouse platelets, Gq is necessary for platelet secretion and aggregation in response to thrombin but is not necessary for thrombin-triggered shape change. G13 appears to contribute to platelet aggregation as well as shape change in response to low concentrations of thrombin but to be unnecessary at higher agonist concentrations; G12 appears to be dispensable for thrombin signaling in platelets. G alpha (q) activates phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides a path to calcium-regulated kinases and phosphatases, GEFs, MAP kinase cassettes and other proteins that mediate cellular responses ranging from granule secretion, integrin activation, and aggregation in platelets. Gbeta:gamma subunits can activate phosphoinositide-3 kinase and other lipid modifying enzymes, protein kinases, and channels. PAR1 activation indirectly leads to activation of cell surface 'sheddases' that liberate ligands for receptor tyrosine kinases, providing a link between thrombin and receptor tyrosine kinases involved in cell growth and differentiation. The pleiotrophic effects of PAR activation are consistent with many of thrombin's diverse actions on cells.More...
Co-activation of P2Y1 and P2Y12 is necessary for complete pl......
Co-activation of P2Y1 and P2Y12 is necessary for complete platelet activation. P2Y1 is coupled to Gq and helps trigger the release of calcium from internal stores, leading to weak and reversible platelet aggregation. P2Y12 is Gi coupled, and required for the amplification of aggregation induced by all platelet agonists including collagen, thrombin, thromboxane, adrenaline and serotonin. P2Y12 activation leads to irreversible platelet aggregation.More...
In the initial response to injury, platelets adhere to damag......
In the initial response to injury, platelets adhere to damaged blood vessels, responding to the exposure of collagen from the vascular epithelium. Once adhered they degranulate, releasing agents such as serotonin and ADP and synthesize Thromboxane A2, all of which amplify the response, recruiting further platelets to the area and promoting platelet aggregation.More...
Co-activation of P2Y1 and P2Y12 is necessary for complete pl......
Co-activation of P2Y1 and P2Y12 is necessary for complete platelet activation. P2Y1 is coupled to Gq and helps trigger the release of calcium from internal stores, leading to weak and reversible platelet aggregation. P2Y12 is Gi coupled, and required for the amplification of aggregation induced by all platelet agonists including collagen, thrombin, thromboxane, adrenaline and serotonin. P2Y12 activation leads to irreversible platelet aggregation.More...
The classical signalling mechanism for G alpha (i) is inhibi......
The classical signalling mechanism for G alpha (i) is inhibition of the cAMP dependent pathway through inhibition of adenylate cyclase. Decreased production of cAMP from ATP results in decreased activity of cAMP-dependent protein kinases.More...
GNB3 related interactors from protein-protein interaction data in HPRD (count: 6)
Basic Information
Positive relationships between GNB3 and other components at different levels (count: 1)
