chemokine (C-C motif) ligand 19 signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by the binding of the C-C chemokine CCL19 to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:nhn, GOC:signaling, PMID:15059845]

The chemokine (C-C motif) ligand 19 (CCL19) signaling pathway is a crucial component of the immune system, primarily involved in the recruitment and activation of immune cells, particularly lymphocytes, to sites of inflammation and infection. This pathway is initiated by the binding of CCL19 to its cognate receptor, CCR7, expressed on the surface of various immune cells, including T cells, B cells, and dendritic cells (DCs).

The interaction of CCL19 with CCR7 triggers a cascade of intracellular signaling events, primarily through the activation of the G protein-coupled receptor (GPCR) signaling pathway. Upon ligand binding, CCR7 undergoes a conformational change, leading to the activation of the associated G protein. This activation results in the dissociation of the G protein subunits, with the alpha subunit activating downstream signaling molecules.

One of the major signaling pathways downstream of CCR7 is the phosphoinositide 3-kinase (PI3K) pathway. Activated G alpha subunits stimulate PI3K, which in turn phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2) to produce phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 acts as a second messenger, recruiting and activating downstream signaling proteins, including Akt and the protein kinase B (PKB).

Akt activation leads to a series of downstream effects, including the regulation of cell survival, proliferation, and migration. Akt also plays a role in the activation of nuclear factor kappa B (NF-κB), a transcription factor that controls the expression of genes involved in inflammation and immune responses.

Another key signaling pathway downstream of CCR7 is the mitogen-activated protein kinase (MAPK) pathway. Activation of the MAPK pathway leads to the phosphorylation and activation of various kinases, including extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs), and p38 kinases. These kinases regulate various cellular processes, including cell growth, differentiation, and apoptosis.

The CCL19 signaling pathway plays a critical role in immune cell trafficking and activation. CCL19 produced by stromal cells and DCs in lymphoid tissues, such as lymph nodes, attracts CCR7-expressing lymphocytes, facilitating their migration from peripheral tissues to lymphoid organs. This process is essential for the initiation of adaptive immune responses.

Furthermore, CCL19 signaling promotes the maturation and activation of DCs. Upon encounter with antigens, DCs migrate to lymph nodes, where they present antigens to T cells. CCL19 signaling in DCs enhances their antigen-presenting capacity and promotes the differentiation of T cells into effector cells.

Overall, the CCL19 signaling pathway is a complex and tightly regulated system that plays a central role in immune homeostasis and the initiation of adaptive immune responses. Its dysregulation has been implicated in the pathogenesis of various inflammatory and autoimmune diseases, highlighting its potential as a therapeutic target for these conditions.'
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Proteins (1)

Compounds (2)