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)

Compounds (19)