positive regulation of cellular response to macrophage colony-stimulating factor stimulus

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of cellular response to macrophage colony-stimulating factor stimulus. [GO_REF:0000058, GOC:BHF, GOC:nc, GOC:TermGenie, PMID:19100238]

Positive regulation of cellular response to macrophage colony-stimulating factor (M-CSF) stimulus is a complex biological process that involves a cascade of molecular events leading to the activation of specific signaling pathways and ultimately the modulation of cellular behavior.

M-CSF, also known as CSF-1, is a cytokine that plays a crucial role in the proliferation, differentiation, and survival of macrophages and their precursors. It exerts its effects by binding to its receptor, the colony-stimulating factor 1 receptor (CSF1R), which is a tyrosine kinase receptor expressed on the surface of these cells.

Upon M-CSF binding, CSF1R undergoes dimerization and autophosphorylation, initiating a signaling cascade that involves the activation of various intracellular signaling molecules, including:

1. **RAS/MAPK Pathway:** Activated CSF1R recruits adapter proteins such as Grb2 and Shc, which in turn activate the Ras GTPase. Ras further activates the MAPK pathway, leading to the phosphorylation and activation of transcription factors such as ERK1/2. This pathway is crucial for cell proliferation, differentiation, and survival.

2. **PI3K/AKT Pathway:** CSF1R also activates the PI3K/AKT pathway by recruiting PI3K to the receptor complex. PI3K catalyzes the production of PIP3, which activates AKT. AKT is a serine/threonine kinase that plays a key role in cell survival, metabolism, and angiogenesis.

3. **STAT Pathway:** CSF1R can also activate the STAT pathway. This pathway is involved in the regulation of gene expression and is essential for the differentiation and function of macrophages.

4. **Calcium Signaling:** M-CSF stimulation can lead to an increase in intracellular calcium levels. This calcium influx activates various calcium-dependent signaling pathways, including the calcineurin pathway, which is involved in the regulation of gene transcription.

These signaling pathways converge to regulate the expression of genes involved in macrophage differentiation, activation, and function. This includes genes encoding for proteins involved in phagocytosis, antigen presentation, cytokine production, and other immune responses.

The positive regulation of cellular response to M-CSF stimulus is therefore crucial for the proper development and function of macrophages, which are essential for host defense against pathogens, tissue repair, and immune homeostasis. Disruptions in this process can lead to various pathological conditions, including autoimmune diseases, inflammatory disorders, and cancer.'
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Proteins (2)

Compounds (7)