Mouse M-CSF R/CD115 Biotinylated Antibody

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). Mouse M-CSF receptor cDNA encodes a 977 amino acid (aa) type I membrane protein with a 19 aa signal peptide, a 492 aa extracellular region containing the ligand-binding domain, a 25 aa transmembrane domain, and a 441 aa cytoplasmic domain. The mouse M-CSF R ECD shares >99% aa identity with rat and 60-63% aa identity with corresponding sequences in human, canine, feline and bovine M-CSF R. 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).