Selected differentially expressed genes in amygdala
Selected differentially expressed genes in amygdala
Positive relationships between PRKAB2 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 PRKAB2 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.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node.
Right-click will show also the menus to link to the report page of the node and remove the node and related edges.
Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web
Negative relationships between PRKAB2 and MDD (count: 0)
Negative relationships between PRKAB2 and other components at different levels (count: 0)
Hypertrophic cardiomyopathy (HCM) is a primary myocardial di......
Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological features of myocyte hypertrophy, myofibrillar disarray, and interstitial fibrosis. HCM is one of the most common inherited cardiac disorders, with a prevalence in young adults of 1 in 500. Hundreds of mutations in 11 genes that encode protein constituents of the sarcomere have been identified in HCM. These mutations increase the Ca2+ sensitivity of cardiac myofilaments. Increased myofilament Ca2+ sensitivity is expected to increase the ATP utilization by actomyosin at submaximal Ca2+ concentrations, which might cause an imbalance in energy supply and demand in the heart under severe stress. The inefficient use of ATP suggests that an inability to maintain normal ATP levels could be the central abnormality. This theory might be supported by the discovery of the role of a mutant PRKAG2 gene in HCM, which in active form acts as a central sensing mechanism protecting cells from depletion of ATP supplies. The increase in the myofilament Ca2+ sensitivity well account for the diastolic dysfunction of model animals as well as human patients of HCM. It has been widely proposed that left ventricular hypertrophy is not a primary manifestation but develops as compensatory response to sarcomere dysfunction.More...
Insulin binding to its receptor results in the tyrosine phos......
Insulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the regulatory subunit of phosphoinositide 3-kinase (PI3K). PI3K activates 3-phosphoinositide-dependent protein kinase 1 (PDK1), which activates Akt, a serine kinase. Akt in turn deactivates glycogen synthase kinase 3 (GSK-3), leading to activation of glycogen synthase (GYS) and thus glycogen synthesis. Activation of Akt also results in the translocation of GLUT4 vesicles from their intracellular pool to the plasma membrane, where they allow uptake of glucose into the cell. Akt also leads to mTOR-mediated activation of protein synthesis by eIF4 and p70S6K. The translocation of GLUT4 protein is also elicited through the CAP/Cbl/TC10 pathway, once Cbl is phosphorylated by INSR. Other signal transduction proteins interact with IRS including GRB2. GRB2 is part of the cascade including SOS, RAS, RAF and MEK that leads to activation of mitogen-activated protein kinase (MAPK) and mitogenic responses in the form of gene transcription. SHC is another substrate of INSR. When tyrosine phosphorylated, SHC associates with GRB2 and can thus activate the RAS/MAPK pathway independently of IRS-1.More...
Increased adipocyte volume and number are positively correla......
Increased adipocyte volume and number are positively correlated with leptin production, and negatively correlated with production of adiponectin. Leptin is an important regulator of energy intake and metabolic rate primarily by acting at hypothalamic nuclei. Leptin exerts its anorectic effects by modulating the levels of neuropeptides such as NPY, AGRP, and alpha-MSH. This leptin action is through the JAK kinase, STAT3 phosphorylation, and nuclear transcriptional effect. Adiponectin lowers plasma glucose and FFAs. These effects are partly accounted for by adiponectin-induced AMPK activation, which in turn stimulates skeletal muscle fatty acid oxidation and glucose uptake. Furthermore, activation of AMPK by adiponectin suppresses endogenous glucose production, concomitantly with inhibition of PEPCK and G6Pase expression. The proinflammatory cytokine TNFalpha has been implicated as a link between obesity and insulin resistance. TNFalpha interferes with early steps of insulin signaling. Several data have shown that TNFalpha inhibits IRS1 tyrosine phosphorylation by promoting its serine phosphorylation. Among the serine/threonine kinases activated by TNFalpha, JNK, mTOR and IKK have been shown to be involved in this phosphorylation.More...
Liver is the major site for carbohydrate metabolism (glycoly......
Liver is the major site for carbohydrate metabolism (glycolysis and glycogen synthesis) and triglyceride synthesis (lipogenesis). While insulin was long thought to be the major regulator of hepatic gene expression, emerging evidence show that nutrients, in particular, glucose and fatty acids, are also able to regulate hepatic genes. This diagram illustrates how glucose metabolite, rather than glucose itself, contributes to the coordinated regulation of carbohydrate and lipid homeostasis in liver through phosphorylation-dependent regulation of ChREBP (carbohydrate responsive element binding protein). ChREBP is a basic helix-loop helix/leucine zipper (bHLH/LZ) transcription factor, shuttling between the cytoplasm and nucleus in a glucose-responsive manner in hepatocytes. When serum glucose is elevated, glucose transporter (GLUT2) and glucokinase (GCK) allow for rapid uptake and equilibration of intracellular glucose levels. This flux of glucose promotes, via the hexose monophosphate shunt pathway (HMP Shunt), the formation of xylulose-5-phosphate (Xu-5-P), which activates protein phosphatase 2A (PP2A) to dephosphorylate ChREBP (Ser196) and promote its nuclear localization. PP2A further dephosphorylates ChREBP in the nucleus, allowing it to dimerize with the bHLH/LZ transcription factor Max-like protein X (MLX) and activate transcription of a number of glycolytic and lipogenic genes containing a ChoRE, such as liver-type pyruvate kinase (L-PK), acetyl-CoA carboxylase 1 (ACACA), and fatty acid synthase (FASN). Upon starvation or high-fat feeding, intrahepatic levels of cAMP and AMP are elevated to activate protein kinase A (PKA) and AMP-dependent protein kinase (AMPK), respectively. PKA-mediated phosphorylation of Thr666 and Ser626 inhibits the DNA binding capacity of ChREBP; so does AMPK-mediated modification of Ser568. PKA-dependent phosphorylation of Ser196 promotes interaction with 14-3-3 and thus sequesters ChREBP in the cytosol. In summary, the phosphorylated form of ChREBP is rendered inactive due to its diminished DNA binding capacity and subcellular compartmentalization. Glucose metabolism triggers dephosphorylation of ChREBP, allowing it to enter the nucleus and activate the transcription of both glycolytic and lipogenic gene expression in liver. The fact that ChREBP/ mice are intolerant to glucose and insulin resistant suggests that ChREBP may also play a role in the pathogenesis of type 2 diabetes.More...
The insulin resistance of type II diabetes appears to be cau......
The insulin resistance of type II diabetes appears to be caused in part by the presence of high levels of lipids in cells such as skeletal muscle where this would not normally be found. The presence of excess lipid stores in skeletal muscle cells interferes with energy metabolism, impairing glucose oxidation and insulin response. Skeletal muscle is one of the primary glucose-consuming tissues, giving it a central role in insulin resistance. The increased risk of diabetes associated with obesity may be caused by increased lipid deposits in skeletal muscle and liver, creating insulin resistance. Leptin is a peptide hormone secreted by adipose tissue that has been associated with many processes. One of the target tissues of leptin is the hypothalamus where it can act to regulate feeding behavior and metabolism. Another leptin target is skeletal muscle. Activation of leptin signaling in skeletal muscle activates the AMP-activated protein kinase (AMP-kinase), known to play a key role in signaling in response to nutrients throughout evolution. AMPK phosphorylates and inactivates the enzyme ACC, acetyl-CoA carboxylase. ACC catalyzes the production of malonyl-CoA from acetyl-CoA. Malonyl-CoA in turn is an inhibitor of the import of fatty acids into mitochondria by carnitine palmitoyl-transferase I for oxidation and energy production. In the presence of leptin, AMPK is activated, ACC is inhibited, and malonyl-CoA levels fall, increasing the oxidation of fatty acids and reducing the lipid content of cells. The reduced lipid content in skeletal muscle allows insulin signaling and glucose consumption to return to their normal levels, reducing insulin resistance.More...
IRS is one of the mediators of insulin signalling events. It......
IRS is one of the mediators of insulin signalling events. It is activated by phosphorylation and triggers a cascade of events involving PI3K, SOS, RAF and the MAP kinases. The proteins mentioned under IRS are examples of IRS family members acting as indicated. More family members are to be confirmed and added in the future.More...
Upon formation of a trimeric LKB1:STRAD:MO25 complex, LKB1 p......
Upon formation of a trimeric LKB1:STRAD:MO25 complex, LKB1 phosphorylates and activates AMPK. If the AMP:ATP ratio rises, this activation is maintained and AMPK activates the TSC complex by phosphorylating TSC2. Active TSC activates the intrinsic GTPase activity of Rheb, resulting in GDP-loaded Rheb and inhibition of mTOR pathway.More...
AMPK plays a central role in regulating fatty acid oxidation......
AMPK plays a central role in regulating fatty acid oxidation in muscle. In order for fatty acids taken up and converted to fatty acyl CoAs by muscle cells to undergo beta-oxidation, they must be transported into the mitochondrial matrix by carnitine palmitoyl transferase. The mitochondrial CPT transport system consists of the malonyl-CoA sensitive carnitine palmitoyltransferase I. In this module, the effect of activated AMPK on fatty acid beta oxidation as mediated by malonyl CoA in muscle cells is annotated. The mechanisms by which leptin and adrenergic receptors modulate AMPK activity will be annotated in the future.More...
LKB1 forms a complex with STRAD and MO25 thereby attaining a......
LKB1 forms a complex with STRAD and MO25 thereby attaining a higher activity towards its substrates belonging to the subfamily of AMPK like kinases. LKB1:STRAD:MO25 complex phosphorylates AMPK constantly. This phosphorylation is immediately removed in basal conditions by PP2C, but if the cellular AMP:ATP ratio rises, binding of AMP by AMPK inhibits the dephosphorylation, and the maintained phosphorylation results in activation of the AMPK.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...
Activated AMPK phosphorylates TSC2 and activates the TSC com......
Activated AMPK phosphorylates TSC2 and activates the TSC complex. TSC2 functions as a GTPase-activating protein and stimulates the intrinsic GTPase activity of a small G-protein Rheb. This results in conversion of Rheb-GTP into Rheb-GDP, and in inhibition of the mTOR activation by GTP-bound Rheb.More...
PRKAB2 related interactors from protein-protein interaction data in HPRD (count: 3)
Basic Information
Positive relationships between PRKAB2 and other components at different levels (count: 1)
