Page last updated: 2024-10-24

negative regulation of platelet-derived growth factor receptor-beta signaling pathway

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of platelet-derived growth factor receptor-beta signaling pathway. [GOC:obol]

The negative regulation of platelet-derived growth factor receptor-beta (PDGFRβ) signaling pathway is a complex process that involves multiple mechanisms to dampen the activity of this crucial pathway in cell growth, proliferation, and differentiation. Here's a breakdown of the key elements involved:

**1. Receptor Tyrosine Kinase (RTK) Inhibition:**
- **Ligand Depletion:** The pathway is initiated by the binding of platelet-derived growth factor (PDGF) to its receptor, PDGFRβ. Reducing PDGF levels by degrading or sequestering it directly impacts the receptor's activation.
- **Competitive Inhibition:** Molecules that bind to the receptor's ligand-binding domain, without activating the receptor, can prevent PDGF from binding.
- **Receptor Internalization and Degradation:** Once activated, PDGFRβ can be internalized into the cell through endocytosis. This process can either lead to receptor recycling back to the cell surface or degradation in lysosomes, effectively reducing the receptor pool available for signaling.

**2. Downstream Signaling Inhibition:**
- **Phosphatase Activity:** Protein tyrosine phosphatases (PTPs) dephosphorylate tyrosine residues on PDGFRβ and downstream signaling molecules, reversing the phosphorylation events essential for pathway activation.
- **Inhibitory Proteins:** Several proteins specifically inhibit key components of the PDGFRβ signaling cascade, including:
- **Sprouty (Spry) Proteins:** Spry proteins interfere with the activation of the Ras/MAPK pathway, a downstream target of PDGFRβ.
- **Phosphoinositide 3-kinase (PI3K) Inhibitors:** These proteins block the activity of PI3K, a crucial mediator of PDGFRβ signaling that is involved in cell survival and growth.
- **SH2 Domain-Containing Phosphatases (SHP):** SHP proteins dephosphorylate and inactivate key signaling molecules, including the adapter protein Grb2, which is involved in downstream signaling cascades.

**3. Transcriptional Regulation:**
- **Transcriptional Repressors:** Several transcription factors can repress the expression of genes involved in PDGFRβ signaling, controlling the production of proteins essential for pathway activation.

**4. Crosstalk with Other Signaling Pathways:**
- The PDGFRβ pathway can be negatively regulated by other signaling pathways, such as the transforming growth factor-beta (TGFβ) pathway, which promotes cell cycle arrest and differentiation, acting as an antagonist to the proliferative signals of PDGFRβ.

**Overall, the negative regulation of PDGFRβ signaling pathway is a complex and tightly regulated process that involves a combination of mechanisms to ensure appropriate cellular responses to growth factors. This regulatory network is critical for maintaining cell homeostasis, preventing uncontrolled proliferation, and contributing to normal tissue development and function.'
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Proteins (3)

ProteinDefinitionTaxonomy
Tyrosine-protein phosphatase non-receptor type 12A tyrosine-protein phosphatase non-receptor type 12 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q05209]Homo sapiens (human)
Tyrosine-protein phosphatase non-receptor type 12A tyrosine-protein phosphatase non-receptor type 12 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q05209]Homo sapiens (human)
Tyrosine-protein phosphatase non-receptor type 2A tyrosine-protein phosphatase non-receptor type 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P17706]Homo sapiens (human)

Compounds (34)

CompoundDefinitionClassesRoles
5-iodo-2-(oxaloamino)benzoic acidorganoiodine compound
lithocholic acidlithocholate : A bile acid anion that is the conjugate base of lithocholic acid.

lithocholic acid : A monohydroxy-5beta-cholanic acid with a alpha-hydroxy substituent at position 3. It is a bile acid obtained from chenodeoxycholic acid by bacterial action.

Lithocholic Acid: A bile acid formed from chenodeoxycholate by bacterial action, usually conjugated with glycine or taurine. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as cholagogue and choleretic.
bile acid;
C24-steroid;
monohydroxy-5beta-cholanic acid
geroprotector;
human metabolite;
mouse metabolite
glycyrrhetinic acidcyclic terpene ketone;
hydroxy monocarboxylic acid;
pentacyclic triterpenoid
immunomodulator;
plant metabolite
oleanolic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid
plant metabolite
vanadatesvanadate(3-) : A vanadium oxoanion that is a trianion with formula VO4 in which the vanadium is in the +5 oxidation state and is attached to four oxygen atoms.

Vanadates: Oxyvanadium ions in various states of oxidation. They act primarily as ion transport inhibitors due to their inhibition of Na(+)-, K(+)-, and Ca(+)-ATPase transport systems. They also have insulin-like action, positive inotropic action on cardiac ventricular muscle, and other metabolic effects.
trivalent inorganic anion;
vanadium oxoanion
EC 3.1.3.1 (alkaline phosphatase) inhibitor;
EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor;
EC 3.1.3.41 (4-nitrophenylphosphatase) inhibitor;
EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor
ursolic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid
geroprotector;
plant metabolite
madecassic acidmonocarboxylic acid;
pentacyclic triterpenoid;
tetrol
antioxidant;
plant metabolite
maslinic acid(2Alpha,3beta)-2,3-dihydroxyolean-12-en-28-oic acid: from Luehea divaricata and Agrimonia eupatoriadihydroxy monocarboxylic acid;
pentacyclic triterpenoid
anti-inflammatory agent;
antineoplastic agent;
antioxidant;
plant metabolite
geniposideterpene glycoside
asiatic acidmonocarboxylic acid;
pentacyclic triterpenoid;
triol
angiogenesis modulating agent;
metabolite
celastrolmonocarboxylic acid;
pentacyclic triterpenoid
anti-inflammatory drug;
antineoplastic agent;
antioxidant;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
Hsp90 inhibitor;
metabolite
cryptotanshinonecryptotanshinone: from Salvia miltiorrhizaabietane diterpenoidanticoronaviral agent
boswellic acidboswellic acid: ursane type; RN given refers to (3alpha,4beta)-isomer; active principle of salai guggal; see also record for salai guggaltriterpenoid
procurcumenolprocurcumenol: RN given for (1S-(1alpha,3abeta,8aalpha))-isomer; epiprocurcumenol is the (1S-(1alpha,3aalpha,8aalpha))-isomer; a TNF-alpha antagonist isolated from Curcuma zedoaria; structure in first sourcesesquiterpenoid
pinocembrin
genipiniridoid monoterpenoidanti-inflammatory agent;
antioxidant;
apoptosis inhibitor;
cross-linking reagent;
hepatotoxic agent;
uncoupling protein inhibitor
2-(oxaloamino)benzoic acid(oxaloamino)benzoic acid
chlorogenic acidcaffeoylquinic acid: Antiviral Agent; structure in first source

chlorogenate : A monocarboxylic acid anion that is the conjugate base of chlorogenic acid; major species at pH 7.3.
cinnamate ester;
tannin
food component;
plant metabolite
tocopherylquinonetocopherylquinone: RN refers to (3R-(3R*,7R*,11R*))-isomer; structure
illudalic acidilludalic acid: isolated from Clitocybe illudens; structure in first source
eupatoriopicrinegermacranolide
morusinmorusin : An extended flavonoid that is flavone substituted by hydroxy groups at positions 5, 2' and 4', a prenyl group at position 3 and a 2,2-dimethyl pyran group across positions 7 and 8.

morusin: from Morus root bark; structure given in first source
extended flavonoid;
trihydroxyflavone
antineoplastic agent;
plant metabolite
trans-2,3',4,5'-tetrahydroxystilbenetrans-2,3',4,5'-tetrahydroxystilbene: hydroxystilbene oxyresveratrolstilbenoid
2-amino-6-chloropurine6-chloroguanine : An organochlorine compound that is 7H-purin-2-amine substituted by a chloro group at position 6.

6-chloroguanine: an antimalarial that inhibits hypoxanthine-guanine-xanthine phosphoribosyltransferase; structure in first source
2-aminopurines;
organochlorine compound
Norartocarpetinflavones
corosolic acidtriterpenoidmetabolite
11-keto-boswellic acid
3-epioleanolic acidtriterpenoidmetabolite
oleanonic acidoleanonic acid: structure in first source
cudraflavanone acudraflavanone A: antineoplastic from Cudrania tricuspidata; structure in first source
zedoarondiolzedoarondiol: structure in first source
formylchromoneformylchromone: structure in first source
rk 682
variabilinvariabilin: an RGD-containing antagonist of glycoprotein IIb-IIIa from the hard tick, Dermacentor variabilis; amino acid sequence given in first source