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Pathways

Showing 1 - 10 of 18 pathways
SMPDB ID Pathway Chemical Compounds Proteins

SMP00749

Pw000726 View Pathway
signaling

Activation of PKC through G protein coupled receptor

Homo sapiens
G protein-coupled receptors sense stimuli outside the cell and transmit signals across the plasma membrane. Activation of protein kinase C (PKC) is one of the common signaling pathways. When a class of GPCRs are activated by a ligand, they activate Gq protein to bind GTP instead of GDP. After the Gq becomes active, it activates phospholipase C (PLC) to cleave the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacyl glycerol (DAG). IP3 is a soluble molecule and is capable of diffusing through the cytoplasm to the ER, where it binds to the Ins3P receptor and opens the calcium channel, releasing the calcium from ER into the cytoplasm. The increases in the concentration of DAG and calcium activate the kinase activity of PKC.

SMP00310

Pw000442 View Pathway
signaling

Corticotropin Activation of Cortisol Production

Homo sapiens
Corticotropin is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is produced from the cleavage of pre-pro-opiomelanocortin by various endopeptidases, along with other physiologically active peptide fragments such as β-lipotropin, γ-lipotropin, Melanocyte Stimulating Hormone (MSH) and β-endorphin. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress. Its principal effects are increased production of androgens and cortisol from the adrenal cortex. The ACTHR receptor activates G(s) proteins which lead to the activation of Adenylyl cyclase which produces the secondary messenger cAMP. cAMP activates PKA (Protein Kinase A) which phosphorylates down stream effectors that lead to androgen and cortisol production.

SMP00308

Pw000440 View Pathway
signaling

Dopamine Activation of Neurological Reward System

Homo sapiens
In the nervous system, dopamine acts as a neurotransmitter with roles in motor control, motivation, arousal, cognition, and reward. The mesolimbic pathway is the main pathway associated with reward, and the dopaminergic neurons of this pathway are found in the substantia nigra (SNc) and ventral tegmental area (VTA) of the midbrain. Dopamine acts on different G protein-coupled receptor subtyes. The D1-class (D1 and D5) receptors stimulate cAMP production by activating adenylyl cyclase, which activates the reward pathway. The D2-class (D2, D3, and D4) subtypes act oppositely, inhibiting cAMP production by inhibiting adenylyl cyclase. The differing distributions of the receptor subtypes mean that complex outputs often produce a synergistic effect, despite the receptor subtypes having opposite molecular effects. References: PMID: 20925949, 21303898

SMP00309

Pw000441 View Pathway
signaling

Excitatory Neural Signalling Through 5-HTR 4 and Serotonin

Homo sapiens
The 5-HT4 receptor is primarily found in the CNS, GI tract and PNS. Peripheral receptors have important roles in the function of many organ responses (alimentary tract, urinary bladder, heart and adrenal gland). Alimentary tract receptors have a role in smooth muscle tone, mucosal electrolyte secretion, and the peristaltic reflex. Urinary Bladder receptors control cholinergic/purinergic transmission. Atrial heart receptors produce positive inotropy and tachycardia that can precipitate arrhythmias. This receptor is also thought to have roles in Anxiety, Appetite, GI Motility, Learning, Memory, Mood, and Respiration. The 5-HT4 receptor activates G(s) proteins which lead to the activation of Adenylyl cyclase which produces the secondary messenger cAMP. cAMP activates PKA (Protein Kinase A) which phosphorylates down stream effectors that lead to a specific cellular response.

SMP00312

Pw000444 View Pathway
signaling

Excitatory Neural Signalling Through 5-HTR 6 and Serotonin

Homo sapiens
The 5-HT6 receptor is primarily expressed in the brain and is involved in glutamatergic and cholinergic neuronal activity. The 5-HT6 receptor activates G(s) proteins which lead to the activation of Adenylyl cyclase which produces the secondary messenger cAMP. cAMP activates PKA (Protein Kinase A) which phosphorylates down stream effectors that lead to a specific cellular response.

SMP00311

Pw000443 View Pathway
signaling

Excitatory Neural Signalling Through 5-HTR 7 and Serotonin

Homo sapiens
The 5-HT7 receptor is primarily found in the CNS, GI tract and Blood Vessels. It is involved in thermoregulation, circadian rhythm, learning and memory, and sleep. It is also speculated that this receptor may be involved in mood regulation. The 5-HT7 receptor activates G(s) proteins which lead to the activation of Adenylyl cyclase which produces the secondary messenger cAMP. cAMP activates PKA (Protein Kinase A) which phosphorylates down stream effectors that lead to a specific cellular response.

SMP00358

Pw000453 View Pathway
signaling

Fc Epsilon Receptor I Signaling in Mast Cells

Homo sapiens
Fc epsilon receptor 1 (Fc epsilon RI) is a high-affinity receptor for the Fc region of immunoglobulin E (IgE), an antibody isotope involved in allergies. The antigens of allergens bind to IgE antibodies, which then interact with Fc epsilon RIs on the surface of mast cells. This activates the mast cells and results in degranulation, a process by which preformed granules containing histamine, proteoglycans, and serine proteases, are released. Activated mast cells also synthesize and secrete lipid-derived mediators (such as prostaglandins, leukotrienes, and platelet-activating factor) and cytokines (notably tumor necrosis factor-alpha, interleukin-4, and interleukin-5). The release of these compounds results in the inflammatory response.

SMP63452

Pw064412 View Pathway
signaling

Histamine H1 Receptor Activation

Homo sapiens
Histamine is a ubiquitous messenger molecule released from mast cells, basophils, enterochromaffin-like cells, and neurons. Its various actions are mediated by histamine receptors H1, H2, H3, and H4. Histamine receptor H1 belongs to the family of G-protein-coupled receptors (GPCRs), and it is expressed in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system. It is linked to an intracellular G-protein (Gαq) that activates phospholipase C and the phosphatidylinositol (PIP2) signalling pathway which promotes inflammatory processes through calcium ion release and expression of the NF-κB immune response transcription factor. H1-antihistamines inactivate the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Upon binding by histamine, the H1 receptor allosterically activates the G-protein by exchanging GDP for GTP at the G-protein's alpha subunit (Gαq). This results in the dissociation of a Gαq-GTP monomer and a Gβγ dimer from the receptor (Wikipedia). Gαq-GTP activates phospholipase C-beta which cleaves the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) into the secondary messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 diffuses through the cytoplasm to the ER and binds to the inositol 1,4,5-trisphosphate (Ins3P) receptor, releasing calcium from the endoplasmic reticulum into the cytoplasm. An increase in the calcium concentration results in increased mediator release and decreased mast cell stability. Both calcium and DAG activate the kinase activity of protein kinase C beta (PKC). Among many other functions, PKC activates NF-κB. This leads to increased antigen presentation and increased expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors.

SMP00391

Pw000454 View Pathway
signaling

Insulin Signalling

Homo sapiens
Insulin is responsible for the regulation of glucose levels in the body. It stimulates the storage of energy and inhibits the breakdown of high energy metabolites. Glycogen and lipid biosynthesis is unregulated and conversely glycogen and Fatty acid metabolism is down regulated. Insulin also modulates transcription and translation. Binding of Insulin to the Insulin receptor (IR) results in the activation of its tryrosine kinase activity leading to IR autophosphorylation. IR then phosphorylates several substrates that lead to the activation of an intracellular signaling cascade. IR activation leads to the activation of H-Ras, MAPK1-3 and PI3-kinase pathways. The activation of these pathways leads to modulation of key proteins in glycogen metabolism / lipid metabolism and transcription / translation.

SMP00320

Pw000445 View Pathway
signaling

Intracellular Signalling Through Adenosine Receptor A2a and Adenosine

Homo sapiens
The A2A receptor is responsible for regulating myocardial blood flow by vasodilating the coronary arteries, which increases blood flow to the myocardium, but may lead to hypotension. The A2A receptor is also expressed in the brain, where it has important roles in the regulation of glutamate and dopamine release. The Adenosine receptor A2a activates G(s) proteins which lead to the activation of Adenylyl cyclase which produces the secondary messenger cAMP. cAMP activates PKA (Protein Kinase A) which phosphorylates down stream effectors that lead to a specific cellular response. This occurs though activation of the MAPK/ERK signaling cascade.
Showing 1 - 10 of 18 pathways