Page last updated: 2024-10-24

negative regulation of macrophage colony-stimulating factor signaling pathway

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of macrophage colony-stimulating factor signaling pathway. [GOC:TermGenie, PMID:16705167]

Negative regulation of macrophage colony-stimulating factor (M-CSF) signaling pathway is a complex process that involves a series of molecular events that suppress the activation of the M-CSF signaling pathway. M-CSF is a growth factor that stimulates the proliferation, differentiation, and survival of macrophages. The M-CSF signaling pathway is initiated when M-CSF binds to its receptor, c-Fms, on the surface of macrophages. This binding event triggers a cascade of intracellular signaling events, ultimately leading to the activation of transcription factors that regulate the expression of genes involved in macrophage function.

The negative regulation of this pathway is crucial for maintaining normal macrophage homeostasis and preventing excessive inflammation. Several mechanisms contribute to the negative regulation of M-CSF signaling, including:

**1. Desensitization of the c-Fms receptor:** Prolonged exposure to M-CSF can lead to desensitization of the c-Fms receptor. This occurs through receptor downregulation, where the receptors are internalized and degraded, or through receptor phosphorylation, which can inhibit receptor signaling.

**2. Inhibitory signaling pathways:** Several intracellular signaling pathways can negatively regulate M-CSF signaling. These pathways include the PI3K/AKT pathway, the MAPK pathway, and the STAT pathway. These pathways can act at different levels in the signaling cascade, inhibiting the activation of downstream signaling molecules.

**3. Expression of inhibitory proteins:** Certain proteins can directly inhibit the M-CSF signaling pathway. For example, the protein SHIP1 can dephosphorylate PIP3, a key signaling molecule in the PI3K pathway, thereby inhibiting PI3K signaling.

**4. Feedback loops:** Negative feedback loops can regulate M-CSF signaling. For example, the transcription factor STAT5, which is activated by M-CSF signaling, can also induce the expression of genes that encode inhibitory proteins, creating a negative feedback loop.

Overall, the negative regulation of M-CSF signaling pathway is a critical process for maintaining macrophage homeostasis and preventing excessive inflammation. This complex process involves various mechanisms, including receptor desensitization, inhibitory signaling pathways, expression of inhibitory proteins, and feedback loops. These mechanisms work together to ensure that M-CSF signaling is appropriately regulated and that macrophages function correctly.'
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Proteins (1)

ProteinDefinitionTaxonomy
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 (30)

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
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
corosolic acidtriterpenoidmetabolite
11-keto-boswellic acid
3-epioleanolic acidtriterpenoidmetabolite
oleanonic acidoleanonic acid: 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