Target type: biologicalprocess
The appearance of any member of the transforming growth factor-beta family of cytokines due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. Transforming growth factor-beta family members include TGF-B1, TGF-B2, and TGF-B3. [GOC:add, GOC:rv, PMID:16891311, PMID:2022183]
Transforming growth factor beta (TGF-β) production is a complex and tightly regulated process that involves multiple cellular signaling pathways and molecular events. TGF-β exists as a latent complex, comprised of a dimeric TGF-β protein bound to a latency-associated protein (LAP). This latent complex is secreted from the cell and remains inactive until activated.
TGF-β activation can occur through various mechanisms:
* **Proteolytic cleavage:** Specific proteases, such as plasmin, MMPs (matrix metalloproteinases), and thrombospondin-1, can cleave LAP, releasing active TGF-β.
* **Integrin-mediated activation:** Integrins, cell surface receptors that bind to extracellular matrix proteins, can interact with LAP and trigger conformational changes that expose the active TGF-β.
* **Acidification:** Changes in pH can disrupt the interaction between TGF-β and LAP, leading to activation.
* **Mechanical stress:** Physical forces, such as shear stress or pressure, can also activate TGF-β.
Once activated, TGF-β can bind to its receptors, TGF-β receptors I and II, on target cells. This binding triggers a cascade of intracellular signaling events, including phosphorylation of downstream signaling molecules, such as Smad proteins. Activated Smads translocate to the nucleus, where they regulate the transcription of target genes involved in various cellular processes, including:
* **Cell proliferation and differentiation:** TGF-β plays a crucial role in regulating cell growth, differentiation, and apoptosis.
* **Extracellular matrix production:** TGF-β promotes the synthesis and deposition of extracellular matrix components, contributing to tissue repair and remodeling.
* **Immune regulation:** TGF-β is a potent immunosuppressive cytokine that modulates immune responses and maintains immune homeostasis.
The production of TGF-β is influenced by a variety of factors, including:
* **Cellular stress:** Factors such as oxidative stress, hypoxia, and DNA damage can stimulate TGF-β production.
* **Cytokines and growth factors:** Other cytokines and growth factors, such as TNF-α, IL-1β, and PDGF, can induce TGF-β expression.
* **Environmental stimuli:** Factors like ultraviolet radiation, mechanical stress, and microbial infections can trigger TGF-β production.
Dysregulation of TGF-β production and signaling is implicated in various pathological conditions, including cancer, fibrosis, autoimmune diseases, and developmental disorders. Therefore, understanding the mechanisms of TGF-β production and regulation is crucial for developing targeted therapies for these diseases.'
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Protein | Definition | Taxonomy |
---|---|---|
Integrin beta-6 | An integrin beta-6 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P18564] | Homo sapiens (human) |
Integrin alpha-V | An integrin alpha-V that is encoded in the genome of human. [PRO:DNx, UniProtKB:P06756] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
1-(3-chlorophenyl)biguanide | 1-(3-chlorophenyl)biguanide: RN given refers to parent cp; a 5-HT3 receptor agonist | biguanides; monochlorobenzenes | |
phenyl biguanide | phenyl biguanide : A member of the class of biguanides that is biguanide in which one of the terminal nitrogen atoms is substituted by a phenyl group. phenyl biguanide: RN given refers to parent cpd | guanidines | central nervous system drug |
4-chlorophenylbiguanide | |||
paclitaxel | Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL). | taxane diterpenoid; tetracyclic diterpenoid | antineoplastic agent; human metabolite; metabolite; microtubule-stabilising agent |
tirofiban | tirofiban : A member of the class of piperidines that is L-tyrosine in which a hydrogen attached to the amino group is replaced by a butylsulfonyl group and in which the hydrogen attached to the phenolic hydroxy group is replaced by a 4-(piperidin-4-yl)butyl group. Tirofiban: Tyrosine analog and PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX antagonist that inhibits PLATELET AGGREGATION and is used in the treatment of ACUTE CORONARY SYNDROME. | L-tyrosine derivative; piperidines; sulfonamide | anticoagulant; fibrin modulating drug; platelet glycoprotein-IIb/IIIa receptor antagonist |
25-hydroxycholesterol | 25-hydroxy steroid; oxysterol | human metabolite | |
tetraiodothyroacetic acid | 3,3',5,5'-tetraiodothyroacetic acid : A monocarboxylic acid that is thyroacetic acid carrying four iodo substituents at positions 3, 3', 5 and 5'. tetraiodothyroacetic acid: RN given refers to parent cpd; structure | 2-halophenol; aromatic ether; iodophenol; monocarboxylic acid | apoptosis inducer; human metabolite; thyroid hormone |
arginyl-glycyl-aspartic acid | arginyl-glycyl-aspartic acid: amino acid sequence of basic unit of widespread cellular recognition system | oligopeptide | |
glycyl-arginyl-glycyl-aspartyl-serine | glycyl-arginyl-glycyl-aspartyl-serine: synthetic peptide from fibronectins; inhibits experimental metastasis of murine melanoma cells | ||
glycyl- arginyl-glycyl-aspartyl-seryl-prolyl-lysine | |||
d-arg-gly-asp-trp | arginyl-glycyl-aspartyl-tryptophan: a synthetic RGD-containing peptide | ||
l 738167 | L 738167: structure in first source | ||
sk&f 107260 | SK&F 107260: structure given in first source | ||
cilengitide | Cilengitide: an alphaVbeta3 integrin antagonist that paralyzes cancer cells | oligopeptide | |
l 734217 | L 734217: fibrinogen receptor antagonist; structure given in first source | ||
elarofiban | elarofiban: a GPIIb and GPIIIa receptor antagonist; structure in first source | ||
eptifibatide | homodetic cyclic peptide; macrocycle; organic disulfide | anticoagulant; platelet aggregation inhibitor | |
arginyl-glycyl-aspartyl-phenylalanine | |||
sb 223245 | |||
cyclic(arg-gly-asp-d-phe-val) | |||
mk-0429 | |||
sb 273005 |