Macrophage colony-stimulating factor
Encyclopedia
Macrophage colony-stimulating factor, or M-CSF, is a secreted cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

 which influences hematopoietic stem cells to differentiate into macrophages or other related cell types. Eukaryotic cells also produce M-CSF in order to combat intercellular viral infection. (See colony-stimulating factor
Colony-stimulating factor
Colony-stimulating factors are secreted glycoproteins that bind to receptor proteins on the surfaces of hemopoietic stem cells, thereby activating intracellular signaling pathways that can cause the cells to proliferate and differentiate into a specific kind of blood cell Colony-stimulating...

.) M-CSF binds to the Colony stimulating factor 1 receptor
Colony stimulating factor 1 receptor
Colony stimulating factor 1 receptor , also known as macrophage colony-stimulating factor receptor , and CD115 , is a cell-surface protein encoded, in humans, by the CSF1R gene...

. It may also be involved in development of the placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...

.

Structure

It is a cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

. The active form of the protein is found extracellularly as a disulfide-linked homodimer, and is thought to be produced by proteolytic cleavage of membrane-bound precursors.

Four transcript variants encoding three different isoforms have been found for this gene.

Function

M-CSF (or CSF-1) is a hematopoietic growth factor that is involved in the proliferation, differentiation, and surival of monocytes, macrophages, and bone marrow progenitor cells. Additionally, high levels of CSF-1 expression are observed in the endometrial epithelium of the pregnant uterus as well as high levels of its receptor CSF1R in the placental trophoblast
Trophoblast
Trophoblasts are cells forming the outer layer of a blastocyst, which provide nutrients to the embryo and develop into a large part of the placenta. They are formed during the first stage of pregnancy and are the first cells to differentiate from the fertilized egg...

. Studies have shown that activation of trophoblasitc CSF1R by local high levels of CSF-1 is essential for normal embryonic implantation and placental development. More recenlty, it was discovered that CSF-1 and its receptor CSF1R are implicated in the mammary gland during normal development and neoplastic growth.

Interactions

Macrophage colony-stimulating factor has been shown to interact
Protein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with PIK3R2
PIK3R2
Phosphatidylinositol 3-kinase regulatory subunit beta is an enzyme that in humans is encoded by the PIK3R2 gene.-Interactions:PIK3R2 has been shown to interact with FYN, HER2/neu, Epidermal growth factor, Cbl gene, PIK3CD, CRKL and Macrophage colony-stimulating factor.-Further reading:...

.
Locally produced M-CSF in the vessel wall contributes to the development and progression of atherosclerosis (Rajavashisth et al http://www.ncbi.nlm.nih.gov/pubmed/9637704)

Further reading

Rajavashisth T, Qiao JH, Tripathi S, Tripathi J, Mishra N, Hua M, Wang XP, Loussararian A, Clinton S, Libby P, Lusis A. Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor- deficient mice. J Clin Invest. 1998 Jun 15;101(12):2702-10.
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