interleukin-16 binding

Definition

Target type: molecularfunction

Binding to interleukin-16. [GOC:jl]

Interleukin-16 (IL-16) is a pleiotropic cytokine primarily known for its role in immune regulation. IL-16 exerts its effects through binding to its cognate receptor, CD4, which is expressed predominantly on T cells, monocytes, and dendritic cells. The molecular function of IL-16 binding to CD4 involves a complex interplay of events that ultimately lead to cellular activation and downstream signaling pathways.

Upon binding to CD4, IL-16 triggers a series of conformational changes in the receptor, leading to the recruitment and activation of intracellular signaling molecules. These signaling events are initiated through the phosphorylation of tyrosine residues within the cytoplasmic tail of CD4. The phosphorylated CD4 serves as a docking site for several adaptor proteins, such as the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 2 (SHP-2), Grb2, and the phosphoinositide 3-kinase (PI3K).

The recruitment and activation of these adaptor proteins trigger distinct signaling pathways:

- SHP-2, a tyrosine phosphatase, dephosphorylates and inhibits signaling molecules involved in T cell activation, such as the TCR complex. This contributes to the immunosuppressive effects of IL-16.

- Grb2, an adaptor protein, binds to the phosphorylated CD4 and acts as a bridge to recruit the son of sevenless (SOS) protein. SOS activates Ras, a small GTPase, which further initiates the mitogen-activated protein kinase (MAPK) pathway. This pathway promotes cell proliferation, differentiation, and survival.

- PI3K, a lipid kinase, generates phosphatidylinositol 3,4,5-trisphosphate (PIP3) at the cell membrane. PIP3 acts as a second messenger, attracting and activating downstream signaling molecules such as Akt, a protein kinase involved in cell survival and growth.

The activation of these signaling pathways ultimately leads to the regulation of various cellular processes, including:

- **T cell chemotaxis:** IL-16 binding to CD4 promotes T cell migration towards sites of inflammation by activating the small GTPase Rho.

- **T cell activation:** IL-16 can both activate and suppress T cell activation depending on the context and other signaling inputs.

- **Cytokine production:** IL-16 influences the production of other cytokines, including interferon-gamma (IFN-γ), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-α).

- **Immunomodulation:** IL-16 plays a crucial role in regulating immune responses, including the suppression of allergic inflammation and the control of autoimmune diseases.

In summary, IL-16 binding to CD4 initiates a cascade of intracellular signaling events that regulate T cell activation, chemotaxis, and cytokine production, ultimately influencing immune homeostasis and inflammatory responses.'
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Proteins (1)

Compounds (1)