Signal transduction

Under development! Ligand Types of ligands Hormones and their receptors Hormone Growth factors Neurotransmitters Receptor Ion channels Chemical communication in arthropods Proton Channels Neuronal Nitric Oxide Synthase (Nos1) is functioning in cell signaling and communication - a vital part of the nervous tissue. Chloride Ion Channel Chloride Intracellular Channel Protein 2 Ivermectin bound to Glu gated chloride channel Membrane Channels & Pumps Ryanodine receptor Lipid signaling: Ceramide Sphingomyelinase (SMase) or sphingomyelin phosphodiesterase is a hydrolase involved in sphingolipid metabolism. It catalyzes the breakdown of sphingomyelin (SM) to phosphocholine and ceramide. Acid-beta-glucosidase or glucosylceramidase is a lysozomal enzyme (EC number 3.2.1.45), which cleaves glucosylceramide to glucose and ceramide. It catalyzes hydrolysis of the sphingolipid, , to at the acidic pH prevailing within the lysosome. . The molecular function of galactosylceramidase is hydrolysis of a O-glycosyl bond to remove galactose from ceramide and other sphingolipids. Sphingosine-1-Phosphate Lysophosphatidic acid receptor#Sphingosine 1-Phosphate Receptor Glucosylceramide Acid-beta-glucosidase Phosphatidylinositol bisphosphate (PIP2) Phosphatidylinositol 4,5-bisphosphate (PIP2) binds to and directly activates inwardly rectifying potassium channels. Inward rectifier KCh. Transient Receptor Potential Cation Channel Subfamily V Member 1 (TRPV1) Phospholipase C beta 3 The Structure of PI3K Epsin Phosphoinositide 3-Kinases PI3K Activation, Inhibition, & Medical Implications Prostaglandins Prostaglandin D synthase Prostaglandin E synthase Cyclooxygenase Prostaglandin-E2 9-reductase Prostaglandin F synthase Leukotriene B4 hydroxydehydrogenase Aldo-keto reductase Endocannabinoids Beta-2 adrenergic receptor Monoglyceride lipase GPR40 Lysophosphatidic acid receptor#Endocannabinoid Receptor 1 Fatty acid amide hydrolase Retinol derivatives Retinal Rhodopsin Rhodopsin Structure and Function The BioMolViz Project Bacteriorhodopsin CRABP I ( Cellular Retinoic Acid Binding Protein ) Retinal dehydrogenase User:Rick H. Cote/PDE6#PDE6: central effector of visual excitation in retinal rod and cone photoreceptors Transducin Pikachurin Retinoid isomerohydrolase Retinoic acid Retinoic acid receptor Cellular retinoic acid-binding protein CRABP I ( Cellular Retinoic Acid Binding Protein ) NK cell receptor Retinoid X receptor RA Mediated T-reg Differentiation PPAR-gamma Student Project 2 for UMass Chemistry 423 Spring 2015 Aldehyde dehydrogenase Steroid Hormones and their receptors This large and diverse class of steroids are biosynthesized from isoprenoids and structurally resemble cholesterol. Mammalian steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens. Vitamin D derivatives are a sixth closely related hormone system with homologous receptors. They have some of the characteristics of true steroids as receptor ligands. For example, is an important estrogen steroid hormone in both women and men. It is a typical steroid with core four-ring system (ABCD), composed of 17 carbon atoms. Corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involved in a wide range of physiological processes. and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect. Glucocorticoids Mineralocorticoids Pentaerythritol tetranitrate reductase active site contains the cofactor and the . Water molecules are shown as red spheres. . Corticosteroid-binding globulin (hydrocortisone) is a corticosteroid with both glucocorticoid and mineralocorticoid activity and effects. Glucocorticoids Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor. is a glucocorticoid medication. It is the most potent glucocorticoid and it has not mineralocorticoid potency. Glucocorticoid receptor. (1m2z). Forkhead box proteins (FOX) are transcription factors involved in regulation of gene expression.. FOXO1 activation contributes to glucocorticoid-induced beta cell death. FOX contain a DNA-binding motif (DBD) of 80-100 amino acids having a winged-helix shape. . . Water molecules shown as red spheres. . Nuclear receptor coactivator (NCOA) is a protein recruited by nuclear receptors in order to enhance or repress DNA transcription. NCOA is involved in coactivation with transcription factors. NCOA1 shows histone acetyltransferase activity and is required for steroid hormone response. NCOA2 is a DNA transcription coactivator with glucocorticoid receptor. . . . Water molecules are shown as red spheres. . . Thioredoxin Reductase (TrxR) is an enzyme which reduces thioredoxin using NADPH. Mutations in TrxR-2 are associated with familial glucocorticoid deficiency. Thioredoxin Reductase (TrxR) is an enzyme which reduces thioredoxin using NADPH. TrxR-2 is mitochondrial. For more details see User:Sarah Abdalla/Thioredoxin Reductase. TrxR and Trx form an . . Water molecules are shown as red spheres. Microsomal Prostaglandin E synthase (PGES) converts cyclooxygenase (COX)-derived prostaglandin to PGE2. It is membrane-associated and belongs to the microsomal glutathione S-transferase family. PGES is preferentially linked with the inducible COX-2 . PGES is induced by proinflammatory stimuli and down-regulated by anti-inflammatory glucocorticoids. Microsomal Prostaglandin E synthase (coordinates are from OPM database. The . Water molecules are shown as red spheres. Mineralocorticoids Mineralocorticoids are a class of corticosteroids. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary mineralocorticoid is . Mineralocorticoid receptor (MR) in epithelial cells is activated by the mineralocorticoid hormone aldosterone promoting renal sodium retention and potassium excretion. It is nuclear receptor. In non epithelial cells MR is activated by cortisol. MR is exposed to many steroids including cortisol, cortisone and progesterone, however, aldosterone and deoxycorticosterone are its physiological ligands. MR mutations are the principal cause of renal pseudohypoaldosteronism. MR mutation S810L causes early-onset hypertension. Inhibition of cardia MR prevents doxorubicin-induced cardiotoxicity. MR is an important proadipogenic transcription factor that may mediate aldosterone and glucocorticoid effects on adipose tissue development and hence on obesity and development of metabolic syndrome. The MR ligand aldosterone binds in a (Alpha Helices, Beta Strands , Loops ,Turns). . . Water molecules are shown as red spheres. Angiotensin-Converting Enzyme, Renin-Angiotensin-Aldosterone System. Hydroxysteroid dehydrogenase Sex steroids Androgens An androgen is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. The major androgen in males is . It is the primary sex hormone and anabolic steroid in males. It is a steroid from the androstane class. It exerts its action through binding to and activation of the androgen receptor. Androgen receptor. Ligand binding domain (LBD) containing an which binds intramolecularly the N-terminal FXXFL motif or coactivators with the same motif. Water molecules are shown as red spheres. (2ylo). Heat shock factor (HSF) are transcriptional activators of heat shock genes. HSF bind to heat shock sequence elements throughout the genome with a consensus array of three oppositely oriented sequence AGGAN and activate transcription. Each HSF monomer contains one C-terminal and 3 N-terminal leucine zippers. Two sequences flanking the N-terminal leucine zippers contain the consensus nuclear localization signal (NLS). The DNA-binding domain (DBD residues 193-281) of HSF lies in the N-terminal of the first NLS region. Depletion of HSF-1 is associated with accumulation of pathogenic androgen receptor in neurodegenerative diseases. Cellular retinoic acid-binding protein (CRABP); Epididymal RABP (ERABP) is an androgen-dependent RABP present in the lumen of the epididymis believed to be involved in sperm maturation. ERABP binds specifically all-trans- and 9-cis-RA. Aromatase. The primary function of aromatase is to produce estrogens by aromatizing androgens. Aromatase is the only known enzyme in vertebrates capable of catalyzing the aromatization of a six-membered ring. Student Project 1 for UMass Chemistry 423 Spring 2015. Protein kinase C related kinase 1 (PRK1) is a component of Rho-GTPase, histone demethylase, androgen receptor, and histone demethylase signaling pathways and is involved in ovary and prostate cancer. A lot of PRK1 is expressed in cases of ovarian serous carcinoma. Finasteride Zolinza (Vorinostat) Hydroxysteroid dehydrogenase, 17-β HSD is involved in the conversion of androstenedione to testosterone. Aromatase converts androstenedione to estrogen and testosterone to estradiol. Lipids: structure and classification Cytochrome P450 3A4 (CYP3A4) Estrogens There are three major endogenous estrogens that have estrogenic hormonal activity: estrone (E1), estradiol (E2), and estriol (E3). Estradiol, an estrane, is the most potent and prevalent. Another estrogen called estetrol (E4) is produced only during pregnancy. Estrogen receptor of estrogen receptor α complexed with raloxifene and a corepressor peptide (morph was taken from Gallery of Morphs of the Yale Morph Server). Structure of estradiol metal chelate and estrogen receptor complex: The basis for designing a new class of SERMs. Selective estrogen receptor modulators, such as estradiol 17-derived metal complexes, have been synthesized as targeted probes for the diagnosis and treatment of breast cancer. The detailed 3D structure of bound with a novel at 2.6Å resolution was reported (2yat). The residues with EPTA-Eu. The hydrogen bonds are shown as white dashed lines. of this structure with the structure of native ligand 17β-estradiol (E2) in the complex of E2/ERα-LBD complex (1ere) reveals that the . The made by additional estrogen receptor residues (e.g. Glu419 of H7 and Glu339 of H3, this depends on subunit), may work together with the E2 17β hydroxyl-His524 hydrogen bond and tighten the neck of the LBP upon binding of the endogenous ligand E2. 4-Hydroxytamoxifen (OHT) is an other selective estrogen receptor modulator. of EPTA-Eu/ERα-LBD complex on OHT/ERα-LBD complex (3ert) shows that there is similar network of hydrogen bonds in both complexes, except for His524 which does not form hydrogen bond with OHT in the OHT/ERα-LBD complex. E2/ERα-LBD (1ere), OHT/ERα-LBD (3ert) and EPTA-Eu/ERα-LBD shows that they overlap well in the majority portions of the domain, but differ significantly in the region of the 'omega loop'. They display different synergistic reciprocating movements, depending on the specific nature of the ligand bound. The structure of estrogen receptor complexed with EPTA-Eu provides important information pertinent to the design of novel functional ER targeted probes for clinical applications. Ivan Koutsopatriy estrogen receptor ER is a modular protein composed of a ligand binding domain, a DNA binding domain and a transactivation domain. ER is a DNA-binding transcription factor. . The DNA binding domain can be clearly observed in this scene; the highlighted yellow helix in close proximity to the DNA is part of the DNA binding domain. The blue beta sheet close to the yellow DNA binding alpha helix is also part of the DNA binding domain. The transactivation domain forms an alpha helix which is colored in purple. The transactivation domain activates RNA polymerase when the receptor binds to DNA. The ligand binding domain may be observed here with the following scene. . The ligand ferutinine (highlighted in pink) is bound by the ligand binding domain, composed of the blue colored alpha helices immediately surrounding the purple ligand. Another view of the ligand binding domain is shown here, with estradiol bound. . ER is functional as a ligand-dependent transcription factor. ER responds to both agonist and antagonist ligands and can associate with the nuclear matrix. Differences in the structure of the receptor are observed depending on what ligand ER has bound (if any). Through comparisons of ER bound to agonist and antagonist ligands, some structural components may be highlighted. The specific conformation of this tight loop of alpha helices and beta sheets around the ligand shows a complex capable of activating ER's transcription loci. This complex allows for the activation signal that will stimulate normal growth. Normal growth is stimulated when an agonist bound ER binds DNA. This occurs with the assistance of chaperon proteins. These chaperons are capable of recognizing estrogen receptor ligand complexes. When ER has bound a ligand chaperons facilitate the trans-location of the complex to the nucleus. Eventually the chaperon ligand ER complex will reach specific euchromatin, at which point the chaperons facilitate the ligand ER complex to changes conformation. This conformation will facilitate the estrogen receptor to bind the DNA major groove at specific palindromic sequences. Estradiol is a normal ligand for ER and allows for binding in the major groove of DNA. If the ligand is an antagonist the transcription factor function of estrogen receptor becomes hindered. The conformation of ER bound to the partial agonist genistein has a loop which is not as tight around the ligand as those found on ER with a complete agonist ligand. The ligands themselves take up different amounts of space and have varying interactions within ER. This slight difference effects the ability of the chaperon to be able to bind the receptor ligand complex to the major groove of DNA. There is a noticeable difference in the size of the pure agonist vs partial agonist scenes. Specifically, look at the width of the agonist compared to the partial agonist. Similar differences may be observed between ER which has bound the partial agonist and complete antagonist ligands. The most drastic difference is noticeable between agonist and antagonist ligands. Compare the agonist scene to the . Special attention should be given to the bottom right alpha helices and beta sheets that are pushed out more in the antagonist compared to the agonist bound ER. Estrogen receptor beta/genistein complex Estrogen receptor beta/p-hydroxybenzene sulfonamide complexes (ER-β) is 1 of the 2 isoforms of the estrogen receptor, a ligand-activated transcription factor which regulates the biological effects of the steroid hormone 17 β-estradiol, or estrogen, in both males and females. The complex is a hetero-tetrameric assembly consisting of 4 molecules and a ligand: 2 copies of , 2 copies of , and the ligand, . Once the ligand is bound, the complex recruits the steroid receptor coactivators, which recruit other proteins to form the transcriptional complex for initiation of transcription. This activates expression of reporter genes containing estrogen response elements. Genistein is a phytoestrogen with structural similarity to estrogen which competes for estrogen receptors. Although estrogen receptor β is widely expressed, it is not the primary estrogen receptor in most tissues. As a result, it has become a target for drug delivery, especially since it is 40x more selective for genistein than the α isoform. This enhanced selectivity may be caused by differences in residues between the 2 isoforms, allowing ER-β to accommodate more polar substituents in its binding pocket. ER-β differs greatly from ER-α at the N-terminal domains, which can be seen located at opposite ends from the C termini in this . The protein is composed of 3 sections: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. N               C Each ERβ contains several domains with specific functions: an N-terminal domain (NTD), a DNA-binding domain (DBD), a flexible hinge region and a C-terminal Ligand-binding domain (LBD). The complex overall is about . The is the 1st activation function (AF-1) domain that consists mostly of random coils and a small portion of helices (red) and sheets (green); it is a . This lack of structure allows the region to recruit and bond many different interaction partners. This region also has the capacity to transactivate transcription without binding estrogen. The binds estrogen response elements (ERE) of target genes and recruits coactivator proteins responsible for the transcription of these genes. The ERE consist of a palindromic inverted repeat 5'GGTCAnnnTGACC-3' of target genes. The DBD is a highly . It is composed of 2 C4-type Zn fingers each containing residues coordinating to a Zn atom. The hinge region connects the DBD and LBD. binds estrogen, coregulatory proteins, corepressors and coactivators. Genistein is not generated by the endocrine system that binds ERβ like estrogen; both ligands are completely buried within the (Hydrophobic, Polar) of the ERβ complex. Binding at the LBD activates transcription mediated by the DBD. This domain is entirely helical; the LBD interacts with genistein through helices. The conformationally dynamic portion of this region gives rise to ERβ’s ligand-dependent transcriptional activation (AF-2) function. A key element of AF-2 is helix 12 (H12), which acts as a conformational switch; different receptor ligands influence the orientation of H12. Agonist ligands like genistein position H12 across the ligand-binding pocket of the LBD, which provides a coactivator docking surface. Geinstein binding allows the helices of AF-2 to form a shallow hydrophobic binding site for leucine-rich motifs of coactivators to bind. This conformation provides optimal interaction with coactivators and transcription is activated. Genistein's bicyclic form allows it to hydrogen bond on opposite sides with the hydroxyls of the histidine groups on the receptor. binding to the receptor causes a conformational change and activates the receptor resulting in up-regulation for coactivators. Down-regulation will occur in the presence of corepressor as they bind to repressors and indirectly regulate gene expression. In order for the estrogen receptor β genistein to bind to a receptor and activate it there must be stabilization by a coactivator. The coactivator increases the gene expression and with this increase allows it to bind to an activator group consisting of a DNA binding domain. The estrogen receptor is found to be comprised of a dimer attached to a ligand and coactivator peptide which helps to stabilize the structure of each monomer. The conformational state of helix-12 can be modified by the binding of the coactivator. This depicts the hydrophobic and hydrophilic residues of the estrogen receptor. The hydrophobic regions are primarily on the inside of the protein surrounding genistein (red). Having the hydrophobic residues surrounding the binding pocket will stabilize the structure. The structure of this pocket is tertiary and do to the hydrophobic interactions inside the pocket and hydrophilic interactions on the outside help to stabilize this tertiary structure. The is hydrophobic which means that an increase in lipophilicity would increase the affinity for ligands which in this case is genistein. The genistein structure has 3 hydroxyl groups, an ether and an ester. These 3 functional groups are polar and have many possibilities for hydrogen bonding. The His475 and Met336 residues in the binding pocket are capable of forming hydrogen bonds with genistein do to the many hydrogen bond forming functional groups. These residues are different from the residues found in ERα and so the selectivity of genistein is much greater for ERβ. Upon visualizing the estrogen receptor in an , the structure can be classified as parallel or anti-parallel. Here is the zoomed . Estrogen-related receptor Tamoxifen and the Estrogen Receptor/Tamoxifen and the Estrogen-related receptor to human estrogen-related receptor γ. The chemotherapeutic drugs bisphenol and are nestled between 4 alpha helices in the ERR active site. Estrogen sulfotransferase Aromatase Finasteride Estrone Estrogen receptor 3D structures Estrone sulfatase Sulfatase 3D structures ABC transporter 3D structures ABCG2 multidrug transporter Substrates, such as estrone sulfate, with residues from each subunit in Cavity 1 of ABCG2 multidrug transporter. Hydroxysteroid dehydrogenase Hydroxysteroid dehydrogenase 3D structures Prostaglandin F synthase Estradiol Lipids: structure and classification Estrogen receptor Ivan Koutsopatriy estrogen receptor Estradiol 17-beta-dehydrogenase Student Project 10 for UMass Chemistry 423 Spring 2015 Aromatase Sulfotransferase ATPase family AAA domain-containing protein 2 Hypoxia-Inducible Factors Estriol Cytochrome P450 3D structures: 1x8v - MtP450 CYP51 (mutant)+estriol Estetrol 3l03 - Crystal Structure of human Estrogen Receptor alpha Ligand-Binding Domain in complex with a Glucocorticoid Receptor Interacting Protein 1 Nr Box II peptide and Estetrol (Estra-1,3,5(10)-triene-3,15 alpha,16alpha,17beta-tetrol) Progestogens Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. Progesterone receptor. (1a28). Water molecules are shown as red spheres. Progesterone is a negative allosteric modulator of nicotinic acetylcholine receptors, and a potent antagonist of the mineralocorticoid receptor. Hydroxysteroid dehydrogenase, 20-α HSD is involved in the control of progesterone level in pregnancy of mice. 17-β HSD is involved in the conversion of androstenedione to testosterone. Vitamin D derivatives; secosteroids (open-ring steroids) . (5ien) Calcitriol is the active form of vitamin D pro-hormone. Vitamin D receptor (also called calcitriol receptor) is a transcription factor. Upon binding to vitamin D, VDR forms a heterodimer with retinoid-X receptor and binds to hormone response receptors on DNA causing gene expression. The (green) binds to receptors in its target cells, controlling the synthesis of many different proteins involved in Ca transport and utilization. . . VDR contains 2 domains: a , that binds to the hormone (grey) and that binds to DNA (green and blue are 2 same VDR structures). It pairs up with a similar protein, 9-cis retinoic acid receptor (RXR), and together they bind to the DNA, activating synthesis in some cases and repressing it in others. When is mutated it is replaced with a which results in an inhibition of transcriptional activation. When transcription is inhibited it results in p53 accumulation, which activates and promotes p53 translocation into mitochondria leading to apoptosis. is replaced with when mutated creating a negative charge. The negative charge at the residue inhibits DNA binding which cause a downregulation of VDR activity. VDR needs DNA binding in order for it to be activated which is only possible with a serine residue. The vitamin D nuclear receptor is a ligand-dependent transcription factor that controls multiple biological responses such as cell proliferation, immune responses, and bone mineralization. Numerous 1 α,25(OH)(2)D(3) analogues, which exhibit low calcemic side effects and/or antitumoral properties, have been synthesized. It was shown that acts as a 1α,25(OH)(2)D(3) superagonist and exhibits both antiproliferative and prodifferentiating properties in vitro. Using this information and on the basis of the crystal structures of human VDR ligand binding domain (hVDR LBD) bound to 1α,25(OH)(2)D(3), 2α-methyl-1α,25(OH)(2)D(3), or 2a, a novel analogue, 2α-methyl-(20S,23S)-epoxymethano-1α,25-dihydroxyvitamin D(3) (4a) was designed, in order to increase its transactivation potency. Signaling Pathways: ABA Signaling Pathway ABA Signaling Pathway PYR/PYL/RCAR family of ABA receptors Protein Phosphatase 2C ABA-regulated SNRK2 Protein Kinase Protein Kinases: Calcium-dependent protein kinase Calcium/Calmodulin-dependent protein kinase Eukaryotic Protein Kinase Catalytic Domain Interleukin-1 receptor-associated kinase Tyrosine kinase Receptor tyrosine kinases Tyrosine kinase Janus kinase or tyrosine-protein kinase JAK (JAK) are nonreceptor tyrosine kinases which transduces cytokine-mediated signals via the JAK-STAT pathway. The JAK-STAT pathway transmits signals through the cell membrane to DNA promoters thus causing transcription. Protein kinase C Protein kinase C The sensitization of TRPV1 is thought to be connected to phosphorylation by protein kinase C and the cleavage of PIP2. MAPK Mitogen-activated protein kinase Mitogen-activated protein kinase kinase Mitogen-activated protein kinase kinase kinase Michael Roberts/BIOL115/ERK2 p38 MAPK (UMass Chem 423 Student Projects 2011-2) CAMP-dependent protein kinase CAMP-dependent protein kinase CAMP Dependent Protein Kinase, Catalytic Subunit Protein Kinase A Chemotaxis: Chemotaxis protein, Histidine Kinase (HK) CheA relays signals from the transmembrane chemoreceptors (methyl-accepting chemotaxis proteins/MCPs) to regulate bacterial chemotaxis. Molecular Playground/Cytoplasmic domain of chemoreceptor of Thermotoga maritima Molecular Playground/Bacterial Chemotaxis Receptors Molecular Playground/cytoplasmic domain of a serine chemotaxis receptor Methyl-accepting chemotaxis protein Mechanotransduction: Fibronectin, Laminin, and Collagen can bind to receptors (integrins). CD44 is a glycoprotein involved in cell-cell interactions. CD44 is a receptor of hyaluronic acid (HA). Mechanosensitive channels are involved in touch, hearing, and in maintaining osmotic balance. Thermoception Heat Shock Proteins Transient receptor potential channels Transient Receptor Potential Cation Channel Subfamily V Member 1 (TRPV1) Voltage-gated channels Voltage-gated calcium channels Voltage-gated calcium channel Cav1.1 complex Potassium Channel Potassium channel toxin Visual phototransduction Light is detected by rhodopsin in rod and cone cells. Rhodopsin#Visual Signal Transduction Rhodopsin Structure and Function Photoreceptor pigments Retinal (in rhodopsin). Rhodopsin#Retinal Chromophore of Rhodopsin and Rhodopsin#Photoisomerization of 11-cis Retinal. Flavin (in cryptochrome). Cryptochrome 4 and JMS/cryptochrome. Circadian clock Circadian clock protein Circadian Clock Protein KaiC Period circadian protein Protein phosphatases: Protein Phosphatase 2C ABA-regulated Protein Phosphatase 2C Second messengers cAMP is second messenger Adenylyl cyclase (ADCY, EC number 4.6.1.1), also known as adenylate cyclase, is an enzyme which catalyzes the cyclization of adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP). Catabolite gene activator protein CAMP-dependent protein kinase CAMP-dependent protein kinase CAMP Dependent Protein Kinase, Catalytic Subunit Protein Kinase A IP3 is second messenger Phospholipase C and PLC beta 3 Gq Receptors that activate this pathway (Phospholipase C) are mainly G protein-coupled receptors coupled to the Gαq subunit, including: 5-HT2 serotonergic receptors (5-hydroxytryptamine receptor#Structural highlights/Specific Function of 5-HT2B). α1 adrenergic receptors Calcitonin receptors Histamine H1 receptor. The H1 receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. The H1 receptor is linked to an intracellular G-protein (Gq) that activates phospholipase C and the inositol triphosphate signaling pathway. When a ligand binds to a G protein-coupled receptor that is coupled to a Gq heterotrimeric G protein, the α-subunit of Gq can bind to and induce activity in the PLC isozyme PLC-β, which results in the cleavage of PIP2 into IP3 and DAG. Metabotropic glutamate receptor 1 and metabotropic glutamate receptor 5 belong to group I and activate phospholipase C. For details see Metabotropic glutamate receptor 5. M1, M3, and M5 muscarinic receptors. Muscarinic acetylcholine receptors (mAChR) contain 5 subtypes M1-M5. Subtypes M1, M3, M5 activate phospholipase C which leads to activation of protein kinase C. Inositol 1,4,5-Trisphosphate Receptor Paracrine signaling: fibroblast growth factor (FGF) family, Hedgehog family, Wnt family, and TGF-β superfamily Fibroblast growth factor and Fibroblast growth factor receptor (FGFR). FGFR belongs to Receptor tyrosine kinases, class V. Sonic Hedgehog Sonic Hedgehog Protein patched homolog 1 (Ptch1) acts as receptor of Sonic Hedgehog protein (Shh) which is involved in formation of embryonic structures. Ca2+ signalling processes Inositol 1,4,5-Trisphosphate Receptor Calcium-dependent protein kinase Calcium/Calmodulin-dependent protein kinase Protein kinase C H+/K+-ATPase signal pathway (acetylcholine, histamine, and gastrin) activates the pump in order to move the vesicles toward the lumen. Esomeprazole and H+/K+ - ATPase Interaction Proton pump Signal transducing adaptor proteins (STAPs) GRB, Growth factor receptor-bound protein and Grb10 SH2 Domain. MyD88, TIR domain-containing adapter protein. GTPase GTPase HRas. The Mitogen-activated protein kinase cascade MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflammatory cytokines. They regulate cell functions including proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis. Mitogen-activated protein kinase Mitogen-activated protein kinase kinase Mitogen-activated protein kinase kinase kinase Michael Roberts/BIOL115/ERK2 p38 MAPK (UMass Chem 423 Student Projects 2011-2) Inflammatory response Aspirin Effects on Cyclooxygenase Cyclooxygenase Interleukin-10 YKL-40 Toll-like Receptors Phospholipase A2 C-X-C motif chemokine Cytokine receptors Allostery Hemoglobin Thrombin Molecular Playground/Caspase-7 Dynamics RNase A Oligomers ATPase ATPase

spinqualitylabelsall models Nicotinic Acetylcholine Receptor, PDB code 2bg9 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image