macrophage migration inhibitory factor signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by macrophage migration inhibitory factor binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:BHF, GOC:signaling, PMID:12782713, PMID:19413900]

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that plays a crucial role in inflammatory and immune responses. It is primarily produced by macrophages, but also by other immune cells, epithelial cells, and endothelial cells. The MIF signaling pathway is complex and involves multiple downstream signaling molecules, leading to a variety of cellular responses.

The MIF signaling pathway is initiated when MIF binds to its receptor, CD74, which is expressed on the surface of various cells. CD74 forms a complex with the transmembrane protein CXCR4, which serves as a co-receptor for MIF. This interaction triggers a cascade of intracellular events, leading to the activation of several signaling pathways.

One of the key signaling pathways activated by MIF is the MAPK pathway. MIF binding to CD74 and CXCR4 activates the MAPKKK, MEKK1, which in turn phosphorylates and activates the MAPKK, MEK. MEK then phosphorylates and activates the MAPK, ERK, which translocates to the nucleus and regulates the expression of target genes involved in inflammation, cell survival, and proliferation.

Another important pathway activated by MIF is the PI3K/AKT pathway. MIF binding to its receptor activates PI3K, which phosphorylates PIP2 to PIP3. PIP3 recruits AKT to the plasma membrane, where it is activated by phosphorylation by PDK1 and mTORC2. Activated AKT promotes cell survival, growth, and metabolism.

MIF also activates the NF-κB pathway, which is a key regulator of inflammatory gene expression. MIF activates the IκB kinase (IKK) complex, leading to phosphorylation and degradation of IκBα. This allows NF-κB to translocate to the nucleus and activate the expression of pro-inflammatory genes, such as TNF-α, IL-6, and IL-1β.

In addition to these signaling pathways, MIF can also activate other signaling molecules, such as STAT3, JNK, and p38 MAPK. The activation of these signaling pathways contributes to the diverse biological effects of MIF, including:

* **Inflammation:** MIF promotes inflammation by activating NF-κB, MAPK, and other signaling pathways, leading to the production of pro-inflammatory cytokines and chemokines.
* **Immune regulation:** MIF plays a role in immune cell activation and differentiation, and it can modulate the immune response to pathogens and allergens.
* **Cell survival and proliferation:** MIF can promote cell survival and proliferation through its activation of the PI3K/AKT pathway and other signaling pathways.
* **Angiogenesis:** MIF can stimulate angiogenesis, the formation of new blood vessels, by activating the MAPK and NF-κB pathways.
* **Tissue repair:** MIF has been implicated in tissue repair and regeneration.

The MIF signaling pathway is a complex and highly regulated process that plays a crucial role in various physiological and pathological processes. Aberrant MIF signaling has been implicated in a number of diseases, including cancer, autoimmune disorders, and inflammatory diseases. Understanding the MIF signaling pathway is essential for developing novel therapeutic strategies targeting MIF-mediated diseases.'
"

Proteins (1)

Compounds (2)