Signal transduction
From Proteopedia
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<StructureSection load='' size='300' side='right' scene='Journal:JBSD:16/Cv/2' caption='Nicotinic Acetylcholine Receptor, PDB code [[2bg9]]'> | <StructureSection load='' size='300' side='right' scene='Journal:JBSD:16/Cv/2' caption='Nicotinic Acetylcholine Receptor, PDB code [[2bg9]]'> | ||
| - | '''Under development!''' | ||
*[[Ligand]] | *[[Ligand]] | ||
*[[Types of ligands]] | *[[Types of ligands]] | ||
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*[[Growth factors]] | *[[Growth factors]] | ||
*[[Neurotransmitters]] | *[[Neurotransmitters]] | ||
| + | *[[Neuropeptides]] | ||
| + | *[[Neuromodulators]] | ||
*[[Receptor]] | *[[Receptor]] | ||
*[[Ion channels]] | *[[Ion channels]] | ||
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*[[Hydroxysteroid dehydrogenase]] | *[[Hydroxysteroid dehydrogenase]] | ||
| - | + | '''[[Sex steroids]]''' | |
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| + | ''[[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 <scene name='89/895670/Cv/5'>testosterone</scene>. 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]]. | 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 <scene name='89/895670/Cv/5'>testosterone</scene>. 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 <scene name='54/543362/Cv/3'>active site</scene> which binds intramolecularly the N-terminal FXXFL motif or coactivators with the same motif.<ref>PMID:18805694</ref> Water molecules are shown as red spheres. <scene name='89/895670/Cv/6'>Human androgen receptor bound to testosterone</scene> ([[2ylo]]). | *[[Androgen receptor]]. Ligand binding domain (LBD) containing an <scene name='54/543362/Cv/3'>active site</scene> which binds intramolecularly the N-terminal FXXFL motif or coactivators with the same motif.<ref>PMID:18805694</ref> Water molecules are shown as red spheres. <scene name='89/895670/Cv/6'>Human androgen receptor bound to testosterone</scene> ([[2ylo]]). | ||
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*Cytochrome P450 3A4 ([[CYP3A4]]) | *Cytochrome P450 3A4 ([[CYP3A4]]) | ||
| - | + | ''[[Estrogens]]'' | |
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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. | 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]] | *[[Estrogen receptor]] | ||
<scene name='Estrogen_receptor/Cv/1'>Click here to see the difference between conformations</scene> of estrogen receptor α complexed with raloxifene and a corepressor peptide (morph was taken from [http://molmovdb.org/cgi-bin/movie.cgi Gallery of Morphs] of the [http://molmovdb.org Yale Morph Server]). | <scene name='Estrogen_receptor/Cv/1'>Click here to see the difference between conformations</scene> of estrogen receptor α complexed with raloxifene and a corepressor peptide (morph was taken from [http://molmovdb.org/cgi-bin/movie.cgi Gallery of Morphs] of the [http://molmovdb.org Yale Morph Server]). | ||
| - | Structure of estradiol metal chelate and estrogen receptor complex: The basis for designing a new class of SERMs<ref>PMID: 21473635</ref>. | ||
| - | 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 <scene name='Journal:JMEDCHEM:1/Cv/11'>estrogen receptor α ligand-binding domain (ER-LBD)</scene> bound with a novel <scene name='Journal:JMEDCHEM:1/Cv/5'>estradiol-derived metal complex, estradiol-pyridinium tetra acetate europium (III) (EPTA-Eu)</scene> at 2.6Å resolution was reported ([[2yat]]). The residues <scene name='Journal:JMEDCHEM:1/Cv/10'>Glu353, Arg394 and His524 and the conserved water molecule (W1006) form hydrogen bonds</scene> with EPTA-Eu. The hydrogen bonds are shown as white dashed lines. <scene name='Journal:JMEDCHEM:1/Cv/7'>Superposition</scene> of this structure with the structure of native ligand 17β-estradiol (E2) in the complex of E2/ERα-LBD complex ([[1ere]]) reveals that the <scene name='Journal:JMEDCHEM:1/Cv/12'>E2 core of EPTA-Eu overlaps closely with that of E2 itself</scene>. The <scene name='Journal:JMEDCHEM:1/Cv/9'>hydrogen bonds network</scene> 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. <scene name='Journal:JMEDCHEM:1/Al/5'>Superposition</scene> 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. <scene name='Journal:JMEDCHEM:1/Al1/3'>Superposition of structures of all these three complexes:</scene> 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. | ||
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| - | <scene name='71/714947/Er_bound_to_dna/4'>ER bound to DNA</scene>. 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. | ||
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| - | <scene name='71/714947/Agonist_ferutinine_bound_er/5'>Agonist ferutinine bound ER</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. <scene name='71/714947/Er_ligand_binding_domain_estra/1'>ER ligand binding domain bound to estradiol</scene>. | ||
| - | 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. <scene name='71/714947/Agonist_estradiol_bound_er/2'>Agonist estradiol bound er</scene> 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. | ||
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| - | 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. | ||
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| - | If the ligand is an antagonist the transcription factor function of estrogen receptor becomes hindered. <scene name='71/714947/Partial_agonist_genistein_er/3'>Partial Agonist genistein bound ER</scene> 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. | ||
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| - | Similar differences may be observed between ER which has bound the partial agonist and complete antagonist ligands. <scene name='71/714947/Antagonist_tamoxifen_bound_er/5'>Antagonist tamoxifen bound ER</scene> The most drastic difference is noticeable between agonist and antagonist ligands. Compare the agonist scene to the <scene name='71/714947/Agonist_estradiol_bound_er/2'>Agonist estradiol bound er</scene>. 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. | ||
| - | *[[Student Project 10 for UMass Chemistry 423 Spring 2015|Estrogen receptor beta/genistein complex]] | ||
| - | *[[Sandbox Reserved 433|Estrogen receptor beta/p-hydroxybenzene sulfonamide complexes]] | ||
| - | <scene name='48/483891/Initial_view/1'>Estrogen receptor β</scene> (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 <scene name='48/483891/Erbeta/1'>estrogen receptor β</scene>, 2 copies of <scene name='48/483891/Steroid_receptor/3'>steroid receptor coactivator-1</scene>, and the ligand, <scene name='48/483891/Ligand/3'>Genistein</scene>. 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. | ||
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| - | 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 <scene name='48/483891/Met336_ile373/2'>336 and 373</scene> 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 <scene name='48/483891/Rainbow/1'>rainbow representation</scene>. The protein is composed of 3 sections: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. | ||
| - | {{Template:ColorKey_N2CRainbow}} | ||
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| - | Each ERβ contains several domains with specific functions: an N-terminal domain (NTD), a {{Template:ColorKey Composition DNA}}-binding domain (DBD), a flexible hinge region and a C-terminal {{Template:ColorKey Composition Ligand}}-binding domain (LBD). The complex overall is about <scene name='48/483891/Erhelices/1'>66% helical (10 helices; 160 residues) and 3% β-sheet (2 strands; 9 residues)</scene>. The <scene name='48/483891/Ntd-erbeta/2'>NTD</scene> 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 <scene name='48/483891/Sequence_conservation/1'>variable region</scene>. 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. | ||
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| - | {{Template:ColorKey_ConSurf_NoYellow}} | ||
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| - | The <scene name='48/483891/Dbdlbd/1'>DBD</scene> 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 <scene name='48/483891/Sequence_conservation/1'>conserved region</scene>. It is composed of 2 C4-type Zn fingers each containing <scene name='48/483891/Dbd-erbeta/4'>4 Cys</scene> residues coordinating to a Zn atom. | ||
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| - | The hinge region connects the DBD and LBD. | ||
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| - | <scene name='48/483891/Dbdlbd/1'>LBD</scene> 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 <scene name='48/483891/Hydrophobic_pocket/3'>hydrophobic core</scene> | ||
| - | ({{Template:ColorKey_Hydrophobic}}, {{Template:ColorKey_Polar}}) of the ERβ complex. | ||
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| - | 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. | ||
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| - | Genistein's bicyclic form allows it to hydrogen bond on opposite sides with the hydroxyls of the histidine groups on the receptor. <scene name='48/483891/Estrogen_kyle/12'>His475's</scene> 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. | ||
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| - | This <scene name='48/483891/Estrogen_kyle/8'>scene</scene> 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 <scene name='48/483891/Estrogen_kyle/16'>binding pocket</scene> 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. | ||
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| - | Upon visualizing the estrogen receptor in an <scene name='48/483891/Arrow_view/1'>arrow representation</scene>, the structure can be classified as parallel or anti-parallel. Here is the zoomed <scene name='48/483891/Hydrophobic_pocket/3'>primarily hydrophobic pocket</scene>. | ||
*[[Estrogen-related receptor]] | *[[Estrogen-related receptor]] | ||
*[[Tamoxifen|Tamoxifen and the Estrogen Receptor/Tamoxifen and the Estrogen-related receptor]] | *[[Tamoxifen|Tamoxifen and the Estrogen Receptor/Tamoxifen and the Estrogen-related receptor]] | ||
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*[[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) | *[[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''' | '''Progesterone''' | ||
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*[[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. | *[[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)''' | |
<scene name='89/895670/Cv/9'>Vitamin D</scene>. | <scene name='89/895670/Cv/9'>Vitamin D</scene>. | ||
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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 <scene name='56/562378/3a3z/1'>the synthetic analogue (20S,23S)-epoxymethano-1α,25-dihydroxyvitamin D(3) (2a)</scene> 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. | 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 <scene name='56/562378/3a3z/1'>the synthetic analogue (20S,23S)-epoxymethano-1α,25-dihydroxyvitamin D(3) (2a)</scene> 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. | ||
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| - | '''Signaling Pathways:''' | ||
''ABA Signaling Pathway'' | ''ABA Signaling Pathway'' | ||
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*[[Protein Phosphatase 2C]] | *[[Protein Phosphatase 2C]] | ||
*[[ABA-regulated SNRK2 Protein Kinase]] | *[[ABA-regulated SNRK2 Protein Kinase]] | ||
| + | |||
| + | '''[[Signaling Pathways]]:''' | ||
| + | *[[Akt/PKB signaling pathway]] | ||
| + | *[[AMPK signaling pathway]] | ||
| + | *[[cAMP-dependent pathway]] | ||
| + | *[[Eph/ephrin signaling pathway]] | ||
| + | *[[Hedgehog signaling pathway]] | ||
| + | *[[Insulin signal transduction pathway]] | ||
| + | *[[JAK-STAT signaling pathway]] | ||
| + | *[[MAPK/ERK pathway]] | ||
| + | *[[mTOR signaling pathway]] | ||
| + | *[[Nodal signaling pathway]] | ||
| + | *[[Notch signaling pathway]] | ||
| + | *[[PI3K/AKT/mTOR signaling pathway]] | ||
| + | *[[TGF beta signaling pathway]] | ||
| + | *[[TLR signaling pathway]] | ||
| + | *[[VEGF signaling pathway]] | ||
| + | *[[Wnt signaling pathway]] | ||
| + | |||
| + | [[MAPK/ERK pathway]] | ||
| + | *[[Mitogen-activated protein kinase]] | ||
| + | *[[Mitogen-activated protein kinase kinase]] | ||
| + | *[[Mitogen-activated protein kinase kinase kinase]] | ||
| + | *[[Michael Roberts/BIOL115/ERK2]] | ||
| + | *[[UMass Chem 423 Student Projects 2011-2#p38 kinase|p38 MAPK (UMass Chem 423 Student Projects 2011-2)]] | ||
'''[[Protein Kinases]]:''' | '''[[Protein Kinases]]:''' | ||
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*[[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. | *The sensitization of [[TRPV1]] is thought to be connected to phosphorylation by [[protein kinase C]] and the cleavage of PIP2. | ||
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| - | ''MAPK'' | ||
| - | *[[Mitogen-activated protein kinase]] | ||
| - | *[[Mitogen-activated protein kinase kinase]] | ||
| - | *[[Mitogen-activated protein kinase kinase kinase]] | ||
| - | *[[Michael Roberts/BIOL115/ERK2]] | ||
| - | *[[UMass Chem 423 Student Projects 2011-2#p38 kinase|p38 MAPK (UMass Chem 423 Student Projects 2011-2)]] | ||
''CAMP-dependent protein kinase'' | ''CAMP-dependent protein kinase'' | ||
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*[[Inositol 1,4,5-Trisphosphate Receptor]] | *[[Inositol 1,4,5-Trisphosphate Receptor]] | ||
| - | Paracrine signaling: | + | '''[[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. | + | *[[Fibroblast growth factor]] and [[Fibroblast growth factor receptor]] (FGFR). FGFR belongs to Receptor tyrosine kinases, class V. |
| + | *[[Hedgehog signaling pathway]] | ||
| + | *[[TGF beta signaling pathway]] | ||
| + | *[[Wnt signaling pathway]] | ||
| - | ''' | + | '''[[Intracrine signaling]]''' |
| - | + | ||
| - | + | ||
| - | '''Ca2+ signalling processes''' | + | '''[[Ca2+ signalling processes]]''' |
*[[Inositol 1,4,5-Trisphosphate Receptor]] | *[[Inositol 1,4,5-Trisphosphate Receptor]] | ||
*[[Calcium-dependent protein kinase]] | *[[Calcium-dependent protein kinase]] | ||
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'''GTPase''' | '''GTPase''' | ||
*[[GTPase HRas]]. | *[[GTPase HRas]]. | ||
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| - | '''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]] | ||
| - | *[[UMass Chem 423 Student Projects 2011-2#p38 kinase|p38 MAPK (UMass Chem 423 Student Projects 2011-2)]] | ||
'''Inflammatory response''' | '''Inflammatory response''' | ||
Current revision
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References
- ↑ Chatterjee S. Neutral sphingomyelinase: past, present and future. Chem Phys Lipids. 1999 Nov;102(1-2):79-96. PMID:11001563
- ↑ Barna TM, Khan H, Bruce NC, Barsukov I, Scrutton NS, Moody PC. Crystal structure of pentaerythritol tetranitrate reductase: "flipped" binding geometries for steroid substrates in different redox states of the enzyme. J Mol Biol. 2001 Jul 6;310(2):433-47. PMID:11428899 doi:10.1006/jmbi.2001.4779
- ↑ Tuteja G, Kaestner KH. SnapShot: forkhead transcription factors I. Cell. 2007 Sep 21;130(6):1160. PMID:17889656 doi:http://dx.doi.org/10.1016/j.cell.2007.09.005
- ↑ Kaiser G, Gerst F, Michael D, Berchtold S, Friedrich B, Strutz-Seebohm N, Lang F, Haring HU, Ullrich S. Regulation of forkhead box O1 (FOXO1) by protein kinase B and glucocorticoids: different mechanisms of induction of beta cell death in vitro. Diabetologia. 2013 Jul;56(7):1587-95. doi: 10.1007/s00125-013-2863-7. Epub 2013, Feb 23. PMID:23435785 doi:http://dx.doi.org/10.1007/s00125-013-2863-7
- ↑ Horwitz KB, Jackson TA, Bain DL, Richer JK, Takimoto GS, Tung L. Nuclear receptor coactivators and corepressors. Mol Endocrinol. 1996 Oct;10(10):1167-77. PMID:9121485 doi:http://dx.doi.org/10.1210/mend.10.10.9121485
- ↑ Arner ES, Holmgren A. Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem. 2000 Oct;267(20):6102-9. PMID:11012661
- ↑ Prasad R, Chan LF, Hughes CR, Kaski JP, Kowalczyk JC, Savage MO, Peters CJ, Nathwani N, Clark AJ, Storr HL, Metherell LA. Thioredoxin Reductase 2 (TXNRD2) mutation associated with familial glucocorticoid deficiency (FGD). J Clin Endocrinol Metab. 2014 Aug;99(8):E1556-63. doi: 10.1210/jc.2013-3844. Epub, 2014 Mar 6. PMID:24601690 doi:http://dx.doi.org/10.1210/jc.2013-3844
- ↑ Arner ES, Holmgren A. Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem. 2000 Oct;267(20):6102-9. PMID:11012661
- ↑ Fritz-Wolf K, Kehr S, Stumpf M, Rahlfs S, Becker K. Crystal structure of the human thioredoxin reductase-thioredoxin complex. Nat Commun. 2011 Jul 12;2:383. doi: 10.1038/ncomms1382. PMID:21750537 doi:10.1038/ncomms1382
- ↑ Murakami M, Nakatani Y, Tanioka T, Kudo I. Prostaglandin E synthase. Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:383-99. PMID:12432931
- ↑ Kudo I, Murakami M. Prostaglandin E synthase, a terminal enzyme for prostaglandin E2 biosynthesis. J Biochem Mol Biol. 2005 Nov 30;38(6):633-8. PMID:16336776
- ↑ Luz JG, Antonysamy S, Kuklish SL, Condon B, Lee MR, Allison D, Yu XP, Chandrasekhar S, Backer R, Zhang A, Russell M, Chang SS, Harvey A, Sloan AV, Fisher MJ. Crystal Structures of mPGES-1 Inhibitor Complexes Form a Basis for the Rational Design of Potent Analgesic and Anti-Inflammatory Therapeutics. J Med Chem. 2015 May 20. PMID:25961169 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b00330
- ↑ Frey FJ, Odermatt A, Frey BM. Glucocorticoid-mediated mineralocorticoid receptor activation and hypertension. Curr Opin Nephrol Hypertens. 2004 Jul;13(4):451-8. PMID:15199296
- ↑ Pujo L, Fagart J, Gary F, Papadimitriou DT, Claes A, Jeunemaitre X, Zennaro MC. Mineralocorticoid receptor mutations are the principal cause of renal type 1 pseudohypoaldosteronism. Hum Mutat. 2007 Jan;28(1):33-40. PMID:16972228 doi:10.1002/humu.20371
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