|Detection of M‑CSF R in Human Blood Monocytes by Flow Cytometry. Human peripheral blood monocytes were stained with Mouse Anti-Human M‑CSF R Alexa Fluor® 700‑conjugated Monoclonal Antibody (Catalog # FAB329N, filled histogram) or isotype control antibody (Catalog # IC002N, open histogram). View our protocol for Staining Membrane-associated Proteins.|
M-CSF receptor, the product of the c-fms proto-oncogene, is a member of the type III subfamily of receptor tyrosine kinases that also includes receptors for SCF and PDGF. These receptors each contain five immunoglobulin-like domains in their extracellular domain (ECD) and a split kinase domain in their intracellular region (1‑4). M-CSF receptor is expressed primarily on cells of the monocyte/macrophage lineage, dendritic cells, stem cells and in the developing placenta (1). Human M-CSF receptor cDNA encodes a 972 amino acid (aa) type I membrane protein with a 19 aa signal peptide, a 493 aa extracellular region containing the ligand-binding domain, a 25 aa transmembrane domain, and a 435 aa cytoplasmic domain. The human M-CSF R ECD shares 60%, 64%, 72%, 75%, 75%, and 76% aa identity with mouse, rat, bovine, canine, feline, and equine M-CSF R, respectively. Activators of protein kinase C induce TACE/ADAM17 cleavage of the M-CSF receptor, releasing the functional ligand-binding extracellular domain (5). M-CSF binding induces receptor homodimerization, resulting in transphosphorylation of specific cytoplasmic tyrosine residues and signal transduction (6). The intracellular domain of activated M-CSF R binds more than 150 proteins that affect cell proliferation, survival, differentiation and cytoskeletal reorganization. Among these, PI3Kinase, P42/44 ERK, and c-Cbl are key transducers of M-CSF R signals (3, 4). M-CSF R engagement is continuously required for macrophage survival and regulates lineage decisions and maturation of monocytes, macrophages, osteoclasts and DC (3, 4). M-CSF R and integrin alpha v beta 3 share signaling pathways during osteoclastogenesis and deletion of either causes osteopetrosis (7, 8). In the brain, microglia expressing increased M-CSF R are concentrated with Alzheimers a beta peptide, but their role in pathogenesis is unclear (9, 10).