CSF-1R/M-CSF-R (E7S2S) Rabbit mAb #14582

Macrophage-colony stimulating factor (M-CSF, CSF-1) receptor is an integral membrane tyrosine kinase encoded by the c-fms proto-oncogene. M-CSF receptor is expressed in monocytes (macrophages and their progenitors) and drives growth and development of this blood cell lineage (1-3). Binding of M-CSF to its receptor induces receptor dimerization, activation, and autophosphorylation of cytoplasmic tyrosine residues used as docking sites for SH2-containing signaling proteins (4). There are at least five major tyrosine autophosphorylation sites. Tyr723 (Tyr721 in mouse) is located in the kinase insert (KI) region. Phosphorylated Tyr723 binds the p85 subunit of PI3 kinase as well as PLCγ2 (5). Phosphorylation of Tyr809 provides a docking site for Shc (5). Overactivation of this receptor can lead to a malignant phenotype in various cell systems (6). The activated M-CSF receptor has been shown to be a predictor of poor outcome in advanced epithelial ovarian carcinoma (7) and breast cancer (8).

After initial dimerization and autophosphorylation, the M-CSF receptor undergoes a regulated intramembrane proteolysis (RIP) involving two cleavage events. Extracellular cleavage of this membrane protein results in release of the extracellular domain, while cleavage in the transmembrane region releases the cytoplasmic domain into the cytosol (9). The activated intracellular domain localizes to the nucleus to regulate transcription of specific pro-inflammatory genes (10). Research studies indicate that the processing and down regulation of M-CSF receptor is a continuous process whose rate increases in response to various stimuli, including PMA, LPS, tumor necrosis factor, IL-2, Il-4, and the physiological ligand M-CSF (9).