Signal transduction
From Proteopedia
(Difference between revisions)
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*[[Phosphoinositide 3-Kinases]] | *[[Phosphoinositide 3-Kinases]] | ||
*[[PI3K Activation, Inhibition, & Medical Implications]] | *[[PI3K Activation, Inhibition, & Medical Implications]] | ||
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| + | '''[[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]] | ||
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| + | '''[[Steroid Hormones and their receptors]]''' | ||
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| + | 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, <scene name='89/895670/Cv/1'>estradiol</scene> 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. | ||
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| + | =[[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. | ||
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| + | <scene name='89/896210/Cv/1'>Prednisone</scene> and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect. | ||
| + | *[[Glucocorticoids]] | ||
| + | *[[Mineralocorticoids]] | ||
| + | *[[Pentaerythritol tetranitrate reductase]] active site contains the cofactor <scene name='49/490063/Cv/5'>FMN</scene> and the <scene name='49/490063/Cv/6'>substrate steroid prednisone</scene><ref>PMID:11428899</ref>. Water molecules are shown as red spheres. <scene name='49/490063/Cv/7'>Whole active site</scene>. | ||
| + | *[[Corticosteroid-binding globulin]] | ||
| + | <scene name='89/895670/Cv/2'>Cortisol</scene> (hydrocortisone) is a corticosteroid with both glucocorticoid and mineralocorticoid activity and effects. | ||
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| + | ==[[Glucocorticoids]]== | ||
| + | Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor. <scene name='89/895670/Cv/3'>Dexamethasone</scene> is a glucocorticoid medication. It is the most potent glucocorticoid and it has not mineralocorticoid potency. | ||
| + | *[[Glucocorticoid receptor]]. <scene name='89/895670/Cv/4'>Human glucocorticoid receptor ligand-binding domain bound to dexamethasone</scene> ([[1m2z]]). | ||
| + | *[[Forkhead box proteins]] (FOX) are transcription factors involved in regulation of gene expression.<ref>PMID:17889656</ref>. '''FOXO1''' activation contributes to '''glucocorticoid'''-induced beta cell death<ref>PMID:23435785</ref>. FOX contain a DNA-binding motif (DBD) of 80-100 amino acids having a winged-helix shape. | ||
| + | **<scene name='47/479231/Cv/5'>Human FoxO1 DNA-binding domain with DNA, Ca+2 and Cl- ions</scene>. | ||
| + | **<scene name='47/479231/Cv/6'>Ca coordination site</scene>. Water molecules shown as red spheres. | ||
| + | **<scene name='47/479231/Cv/7'>Cl coordination site</scene>. | ||
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| + | *[[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<ref>PMID:9121485</ref>. '''NCOA1''' shows histone acetyltransferase activity and is required for '''steroid hormone''' response. '''NCOA2''' is a DNA transcription coactivator with '''glucocorticoid''' receptor. | ||
| + | **<scene name='49/494427/Cv/7'>NCOA/STAT6 transactivator domain LXXLL peptide interactions</scene>. | ||
| + | **<scene name='49/494427/Cv/8'>1st Iod coordination site</scene>. | ||
| + | **<scene name='49/494427/Cv/9'>2nd Iod coordination site</scene>. Water molecules are shown as red spheres. | ||
| + | **<scene name='49/494427/Cv/10'>3th and 4th Iod coordination sites</scene>. | ||
| + | **<scene name='49/494427/Cv/11'>5th Iod coordination site</scene>. | ||
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| + | *[[Thioredoxin Reductase]] (TrxR) is an enzyme which reduces thioredoxin using NADPH<ref>PMID:11012661</ref>. Mutations in TrxR-2 are associated with familial '''glucocorticoid''' deficiency<ref>PMID:24601690</ref>. Thioredoxin Reductase (TrxR) is an enzyme which reduces thioredoxin using NADPH<ref>PMID:11012661</ref>. '''TrxR-2''' is mitochondrial. For more details see [[User:Sarah Abdalla/Thioredoxin Reductase]]. TrxR and Trx form an <scene name='43/433123/Cv/6'>intramolecular Cys-Cys bond</scene><ref>PMID:21750537</ref>. <scene name='43/433123/Cv/7'>FAD binding site</scene>. Water molecules are shown as red spheres. | ||
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| + | *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<ref>PMID:12432931</ref> . PGES is induced by proinflammatory stimuli and down-regulated by anti-inflammatory '''glucocorticoids'''<ref>PMID:16336776</ref>. Microsomal ''Prostaglandin E synthase'' <scene name='77/778890/Cv/2'>is membrane-associated</scene> (coordinates are from [http://opm.phar.umich.edu/protein.php?extrapdb=4yl0 OPM database]. The <scene name='77/778890/Cv/6'>anti-inflammatory inhibitor binds to PGES in a pocket above the glutathione and interacts with various side-chains of a helix</scene><ref>PMID:25961169</ref>. Water molecules are shown as red spheres. | ||
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| + | ==[[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 <scene name='89/896192/Cv/1'>aldosterone</scene>. | ||
| + | *[[Mineralocorticoid receptor]] (MR) in epithelial cells is activated by the mineralocorticoid hormone aldosterone promoting renal sodium retention and potassium excretion. It is [[Nuclear receptors|nuclear receptor]]. In non epithelial cells MR is activated by cortisol<ref>PMID:15199296</ref>. 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<ref>PMID:16972228</ref>. MR mutation S810L causes early-onset hypertension<ref>PMID:10884226</ref>. Inhibition of cardia MR prevents doxorubicin-induced cardiotoxicity<ref>PMID:28430882</ref>. 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<ref>PMID:17384139</ref>. The MR ligand aldosterone binds in a <scene name='78/781019/Cv/6'>fully enclosed pocket, contacting residues with six α-helices and a β-turn</scene> ({{Template:ColorKey_Helix}},{{Template:ColorKey_Strand}},{{Template:ColorKey_Loop}},{{Template:ColorKey_Turn}}). <scene name='78/781019/Cv/7'>It forms hydrogen bonds with 4 MR residues</scene><ref>PMID:15967794</ref>. <scene name='78/781019/Cv/8'>Whole binding site</scene>. Water molecules are shown as red spheres. | ||
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| + | *[[Angiotensin-Converting Enzyme]], Renin-Angiotensin-Aldosterone System. | ||
| + | *[[Hydroxysteroid dehydrogenase]] | ||
*[[Lysophosphatidic acid receptor]] | *[[Lysophosphatidic acid receptor]] | ||
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*[[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. | *[[Protein patched homolog 1]] (Ptch1) acts as receptor of Sonic Hedgehog protein (Shh) which is involved in formation of embryonic structures. | ||
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'''Ca2+ signalling processes''' | '''Ca2+ signalling processes''' | ||
Revision as of 14:53, 15 December 2021
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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
- ↑ Geller DS, Farhi A, Pinkerton N, Fradley M, Moritz M, Spitzer A, Meinke G, Tsai FT, Sigler PB, Lifton RP. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science. 2000 Jul 7;289(5476):119-23. PMID:10884226
- ↑ Lother A, Bergemann S, Kowalski J, Huck M, Gilsbach R, Bode C, Hein L. Inhibition of the cardiac myocyte mineralocorticoid receptor ameliorates doxorubicin-induced cardiotoxicity. Cardiovasc Res. 2018 Feb 1;114(2):282-290. doi: 10.1093/cvr/cvx078. PMID:28430882 doi:http://dx.doi.org/10.1093/cvr/cvx078
- ↑ Caprio M, Feve B, Claes A, Viengchareun S, Lombes M, Zennaro MC. Pivotal role of the mineralocorticoid receptor in corticosteroid-induced adipogenesis. FASEB J. 2007 Jul;21(9):2185-94. doi: 10.1096/fj.06-7970com. Epub 2007 Mar 23. PMID:17384139 doi:http://dx.doi.org/10.1096/fj.06-7970com
- ↑ Bledsoe RK, Madauss KP, Holt JA, Apolito CJ, Lambert MH, Pearce KH, Stanley TB, Stewart EL, Trump RP, Willson TM, Williams SP. A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor. J Biol Chem. 2005 Sep 2;280(35):31283-93. Epub 2005 Jun 20. PMID:15967794 doi:http://dx.doi.org/10.1074/jbc.M504098200
