Signal transduction: Difference between revisions
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*[[Hydroxysteroid dehydrogenase]] | *[[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 <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]]'' | |||
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]] | ||
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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>. | ||
Revision as of 15:01, 15 December 2021
Under development!
Sphingosine-1-Phosphate Glucosylceramide Phosphatidylinositol bisphosphate (PIP2) Phosphatidylinositol 4,5-bisphosphate (PIP2) binds to and directly activates inwardly rectifying potassium channels. Inward rectifier KCh.
Retinal
Retinoic acid
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, estradiol 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 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. Prednisone and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect.
Cortisol (hydrocortisone) is a corticosteroid with both glucocorticoid and mineralocorticoid activity and effects. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor. Dexamethasone is a glucocorticoid medication. It is the most potent glucocorticoid and it has not mineralocorticoid potency.
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 aldosterone.
Sex steroids 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 testosterone. 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.
[[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. Click here to see the difference between conformations of estrogen receptor α complexed with raloxifene and a corepressor peptide (morph was taken from Gallery of Morphs of the Yale Morph Server).
Binding of nuclear receptor corepressor 2 peptide and 4-hydroxytamoxifen to human estrogen-related receptor γ. The chemotherapeutic drugs bisphenol and tamoxifen are nestled between 4 alpha helices in the ERR active site. Estrone
Substrates, such as estrone sulfate, form hydrogen bonds and stacking interactions with residues from each subunit in Cavity 1 of ABCG2 multidrug transporter. Estradiol
Estriol
Estetrol
Progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species.
Vitamin D derivatives; secosteroids (open-ring steroids) 25-hydroxy-cholecalciferol (25-D3); 25-hydroxyvitamin D3 (5ien) Calcitriol is the active form of vitamin D pro-hormone.
Vitamin D receptor (VDR) 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 vitamin D hormone (green) binds to receptors in its target cells, controlling the synthesis of many different proteins involved in Ca transport and utilization. Vitamin D hormone binding site. Vitamin D hormone is located in deep pocket. VDR contains 2 domains: a ligand binding domain (LBD), that binds to the hormone (grey) and DNA-binding domain (DBD) 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 serine is mutated it is replaced with a glycine 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. Serine is replaced with aspartic acid 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 the synthetic analogue (20S,23S)-epoxymethano-1α,25-dihydroxyvitamin D(3) (2a) 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
Tyrosine kinase
Protein kinase C
MAPK
CAMP-dependent protein kinase
Transient receptor potential channels
Light is detected by rhodopsin in rod and cone cells.
Protein phosphatases: Second messengers
CAMP-dependent protein kinase Receptors that activate this pathway (Phospholipase C) are mainly G protein-coupled receptors coupled to the Gαq subunit, including:
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
Ca2+ signalling processes
H+/K+-ATPase signal pathway (acetylcholine, histamine, and gastrin) activates the pump in order to move the vesicles toward the lumen. Proton pump Signal transducing adaptor proteins (STAPs)
GTPase 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.
Inflammatory response
Allostery ATPase
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