cellular response to granulocyte macrophage colony-stimulating factor stimulus

Definition

Target type: biologicalprocess

Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a granulocyte macrophage colony-stimulating factor stimulus. [GOC:BHF, GOC:ebc, PMID:7901744]

Granulocyte macrophage colony-stimulating factor (GM-CSF) is a cytokine that plays a crucial role in the production, differentiation, and activation of granulocytes (neutrophils, eosinophils, and basophils) and macrophages. Its signaling pathway is initiated when GM-CSF binds to its receptor complex, composed of the α and β chains. This binding event triggers a cascade of intracellular events, ultimately leading to the activation of various signaling pathways, including the JAK-STAT, MAPK, and PI3K pathways.

The JAK-STAT pathway is activated upon GM-CSF binding, resulting in the phosphorylation of JAK kinases. These phosphorylated JAKs subsequently phosphorylate the receptor's cytoplasmic tail, creating docking sites for STAT proteins. STAT proteins bind to the phosphorylated receptor and become phosphorylated themselves. Phosphorylated STATs dimerize and translocate to the nucleus, where they bind to specific DNA sequences, activating gene expression.

The MAPK pathway is activated by the phosphorylation of Ras GTPase. Activated Ras triggers a signaling cascade involving Raf, MEK, and ERK kinases. Phosphorylated ERK translocates to the nucleus and phosphorylates transcription factors, influencing gene expression related to cell proliferation, differentiation, and survival.

The PI3K pathway is initiated by the activation of PI3K, which phosphorylates phosphatidylinositol lipids. These phosphorylated lipids recruit signaling molecules, such as AKT and mTOR, to the membrane. Activated AKT promotes cell survival and growth by phosphorylating downstream targets, including Bad and FoxO transcription factors. mTOR, on the other hand, regulates protein synthesis and cell growth.

The activation of these signaling pathways by GM-CSF leads to a wide range of biological effects. It stimulates the production of granulocytes and macrophages from their precursors in the bone marrow. It enhances the survival, proliferation, and differentiation of these cells. It also promotes their activation, enhancing their ability to phagocytose pathogens, produce reactive oxygen species, and secrete cytokines.

Furthermore, GM-CSF plays a role in regulating inflammation and immune responses. It promotes the recruitment of immune cells to sites of inflammation and enhances their ability to clear pathogens. It also contributes to the development of adaptive immune responses by promoting the differentiation of T helper cells.

In summary, the cellular response to GM-CSF stimulus involves a complex interplay of signaling pathways, leading to the activation and differentiation of granulocytes and macrophages. This process is essential for maintaining immune homeostasis and defending the body against pathogens.'
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Proteins (4)

Compounds (319)