Page last updated: 2024-10-24

CD40 signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by the binding of the cell surface receptor CD40 to one of its physiological ligands, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:mtg_signal, GOC:signaling, PMID:11348017]

The CD40 signaling pathway is a crucial component of the immune system, playing a vital role in B cell activation, antibody production, and immune regulation. It is initiated when CD40, a transmembrane receptor expressed on B cells, antigen-presenting cells (APCs), and other immune cells, engages with its ligand, CD40 ligand (CD40L), which is expressed on activated T cells, particularly helper T cells (Th cells).

Upon CD40-CD40L interaction, a cascade of intracellular signaling events is triggered. This begins with the recruitment of adaptor proteins, such as TRAF2, TRAF3, and TRAF6, to the cytoplasmic tail of CD40. These adaptor proteins then activate downstream signaling pathways, primarily the NF-κB pathway and the MAPK (mitogen-activated protein kinase) pathway.

The NF-κB pathway, a key regulator of immune responses, is activated by the ubiquitination and proteasomal degradation of inhibitory proteins, such as IκBα. This allows NF-κB to translocate to the nucleus, where it promotes the transcription of genes involved in B cell activation, proliferation, and differentiation, including genes encoding cytokines such as IL-6, IL-10, and TNF-α.

The MAPK pathway, a cascade of protein kinases, is activated by the phosphorylation of MAPK kinases (MKKs), which in turn phosphorylate MAPKs, such as ERK, JNK, and p38. These MAPKs influence various cellular processes, including cell proliferation, differentiation, and survival.

The activation of the CD40 signaling pathway has several important consequences for the immune system:

- B cell activation: CD40 signaling is essential for B cell activation and differentiation into antibody-secreting plasma cells.
- Antibody production: CD40 engagement enhances antibody production by promoting class switch recombination (CSR) and affinity maturation.
- Immune regulation: CD40 signaling plays a role in regulating immune responses by modulating the production of cytokines and the activation of T cells.
- Antigen presentation: CD40 signaling enhances the ability of APCs to present antigens to T cells, further promoting immune responses.

In addition to its role in immunity, CD40 signaling has been implicated in various pathological processes, including autoimmune diseases, cancer, and inflammation. Dysregulation of CD40 signaling can lead to excessive immune activation and inflammation, contributing to the development of these diseases.

Therefore, the CD40 signaling pathway is a highly complex and tightly regulated process that plays a fundamental role in immune responses and a wide range of physiological and pathological processes.'
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Proteins (3)

ProteinDefinitionTaxonomy
E3 ubiquitin-protein ligase RNF31An E3 ubiquitin-protein ligase RNF31 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q96EP0]Homo sapiens (human)
Integrin alpha-5An integrin alpha-5 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P08648]Homo sapiens (human)
Integrin beta-1An integrin beta-1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P05556]Homo sapiens (human)

Compounds (19)

CompoundDefinitionClassesRoles
bupropionbupropion : An aromatic ketone that is propiophenone carrying a tert-butylamino group at position 2 and a chloro substituent at position 3 on the phenyl ring.

Bupropion: A propiophenone-derived antidepressant and antismoking agent that inhibits the uptake of DOPAMINE.
aromatic ketone;
monochlorobenzenes;
secondary amino compound
antidepressant;
environmental contaminant;
xenobiotic
haloperidolhaloperidol : A compound composed of a central piperidine structure with hydroxy and p-chlorophenyl substituents at position 4 and an N-linked p-fluorobutyrophenone moiety.

Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)
aromatic ketone;
hydroxypiperidine;
monochlorobenzenes;
organofluorine compound;
tertiary alcohol
antidyskinesia agent;
antiemetic;
dopaminergic antagonist;
first generation antipsychotic;
serotonergic antagonist
gliotoxingliotoxin : A pyrazinoindole with a disulfide bridge spanning a dioxo-substituted pyrazine ring; mycotoxin produced by several species of fungi.

Gliotoxin: A fungal toxin produced by various species of Trichoderma, Gladiocladium fimbriatum, Aspergillus fumigatus, and Penicillium. It is used as an immunosuppressive agent.
dipeptide;
organic disulfide;
organic heterotetracyclic compound;
pyrazinoindole
antifungal agent;
EC 2.5.1.58 (protein farnesyltransferase) inhibitor;
immunosuppressive agent;
mycotoxin;
proteasome inhibitor
1,3-ditolylguanidine1,3-ditolylguanidine: structure given in first source; a selective ligand for the sigma binding sites in the braintoluenes
tirofibantirofiban : 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
arginyl-glycyl-aspartic acidarginyl-glycyl-aspartic acid: amino acid sequence of basic unit of widespread cellular recognition systemoligopeptide
arginyl-glycyl-aspartyl-serinearginyl-glycyl-aspartyl-serine: corresponds to cell attachment site of fibronectin; located near carboxyl-terminal region of alpha-chain of fibrinogen; inhibits platelet aggregation & fibrinogen binding to activated platelets
glycyl-arginyl-glycyl-aspartyl-serineglycyl-arginyl-glycyl-aspartyl-serine: synthetic peptide from fibronectins; inhibits experimental metastasis of murine melanoma cells
d-arg-gly-asp-trparginyl-glycyl-aspartyl-tryptophan: a synthetic RGD-containing peptide
l 738167L 738167: structure in first source
cilengitideCilengitide: an alphaVbeta3 integrin antagonist that paralyzes cancer cellsoligopeptide
l 734217L 734217: fibrinogen receptor antagonist; structure given in first source
cyclopaminepiperidinesglioma-associated oncogene inhibitor
arginyl-glycyl-aspartyl-phenylalanine
cyclic(arg-gly-asp-d-phe-val)
mk-0429
mocetinostatmocetinostat : A benzamide obtained by formal condensation of the carboxy group of 4-({[4-(pyridin-3-yl)pyrimidin-2-yl]amino}methyl)benzoic acid with one of the amino groups of benzene-1,2-diamine. It is an orally active and isotype-selective HDAC inhibitor which exhibits antitumour activity (IC50 = 0.15, 0.29, 1.66 and 0.59 muM for HDAC1, HDAC2, HDAC3 and HDAC11).

mocetinostat: undergoing phase II clinical trials for treatment of cancer
aminopyrimidine;
benzamides;
pyridines;
secondary amino compound;
secondary carboxamide;
substituted aniline
antineoplastic agent;
apoptosis inducer;
autophagy inducer;
cardioprotective agent;
EC 3.5.1.98 (histone deacetylase) inhibitor;
hepatotoxic agent
tr 14035N-(2,6-dichlorobenzoyl)-4-(2',6'-bismethoxyphenyl)phenylalanine: TR-14035 is the (L)-isomer; an antagonist of both alpha4beta1 and beta7 integrins; structure in first source
bio 1211BIO 1211: integrin alpha4beta1 inhibitor; structure in first source