response to macrophage colony-stimulating factor

Definition

Target type: biologicalprocess

Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a macrophage colony-stimulating factor stimulus. [GOC:yaf, PMID:14687666]

Macrophage colony-stimulating factor (M-CSF) is a cytokine that plays a critical role in the development, survival, and function of macrophages. The response to M-CSF is a complex process that involves multiple signaling pathways and downstream effector molecules.

1. **Binding and Receptor Dimerization:** M-CSF binds to its receptor, the colony-stimulating factor 1 receptor (CSF1R), which is a transmembrane tyrosine kinase receptor. This binding induces dimerization of CSF1R, bringing two receptor molecules together.

2. **Activation of Tyrosine Kinase Activity:** Dimerization activates the tyrosine kinase activity of CSF1R, leading to autophosphorylation of the receptor on specific tyrosine residues.

3. **Recruitment of Signaling Adapters:** Phosphorylated tyrosine residues on CSF1R act as docking sites for various signaling adaptor proteins, including Src homology 2 (SH2) domain-containing proteins like Grb2 and Gab2.

4. **Activation of Ras/MAPK and PI3K/AKT Pathways:**
- The recruitment of Grb2 and Gab2 initiates the Ras/MAPK pathway, leading to activation of ERK, JNK, and p38 MAP kinases.
- The PI3K/AKT pathway is activated by the recruitment of PI3K to the receptor complex. PI3K phosphorylates PIP2, converting it to PIP3, which activates AKT.

5. **Transcriptional Regulation:** The activated MAPK and AKT pathways converge on transcription factors, such as NF-κB, AP-1, and STAT5. These transcription factors regulate the expression of genes involved in macrophage proliferation, survival, differentiation, and function.

6. **Macrophage Differentiation and Function:** M-CSF signaling promotes the differentiation of monocytes into macrophages. Macrophages are essential for innate immunity, phagocytosis of pathogens and cellular debris, tissue repair, and antigen presentation.

7. **Survival and Proliferative Signals:** M-CSF also provides survival signals for macrophages, preventing their apoptosis. It further promotes macrophage proliferation, contributing to the maintenance of macrophage populations in tissues.

8. **Regulation of Macrophage Activity:** The response to M-CSF is tightly regulated by various mechanisms, including negative feedback loops, cross-talk with other signaling pathways, and the presence of other cytokines and growth factors in the microenvironment.'
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Proteins (2)

Compounds (29)