| Function: |
Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding. Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor. |
| Tissue Specificity: |
Expressed in bone marrow and in differentiated blood mononuclear cells. |
| Involvement in Disease: |
Leukoencephalopathy, diffuse hereditary, with spheroids: An autosomal dominant *****-onset rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often die of dementia within 6 years of onset. Brain imaging shows patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes. |
| Sequence Similarities: |
Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. |
| Post-Translational Modification: |
Autophosphorylated in response to CSF1 or IL34 binding. Phosphorylation at Tyr-561 is important for normal down-regulation of signaling by ubiquitination, internalization and degradation. Phosphorylation at Tyr-561 and Tyr-809 is important for interaction with SRC family members, including FYN, YES1 and SRC, and for subsequent activation of these protein kinases. Phosphorylation at Tyr-699 and Tyr-923 is important for interaction with GRB2. Phosphorylation at Tyr-723 is important for interaction with PIK3R1. Phosphorylation at Tyr-708 is important for normal receptor degradation. Phosphorylation at Tyr-723 and Tyr-809 is important for interaction with PLCG2. Phosphorylation at Tyr-969 is important for interaction with CBL. Dephosphorylation by PTPN2 negatively regulates downstream signaling and macrophage differentiation. |
| Cellular Location: |
Cell membrane. |
| Database Links: |
Entrez Gene: 1436?HumanOmim: 164770?HumanSwissProt: P07333?HumanUnigene: 586219?Human |
| Synonyms: |
C FMS AntibodyCD 115 AntibodyCD115 AntibodyCD115 antigen AntibodyCFMS AntibodyColony stimulating factor 1 receptor AntibodyColony stimulating factor I receptor AntibodyCSF 1 R AntibodyCSF 1R AntibodyCSF-1 receptor AntibodyCSF-1-R AntibodyCSF1 R AntibodyCSF1R AntibodyCSF1R_HUMAN AntibodyCSFR AntibodyEC 2.7.10.1 AntibodyFIM 2 AntibodyFIM2 AntibodyFMS AntibodyFMS proto oncogene AntibodyFMS protooncogene AntibodyHDLS AntibodyM-CSF Receptor AntibodyM-CSF-R AntibodyMacrophage colony stimulating factor 1 receptor AntibodyMacrophage colony stimulating factor I receptor AntibodyMacrophage colony-stimulating factor 1 receptor AntibodyMcDonough feline sarcoma viral (v fms) oncogene homolog AntibodyMCSF Receptor AntibodyMCSFR AntibodyOncogen FMS AntibodyProto-oncogene c-Fms AntibodyV-FMS McDonough feline sarcoma viral oncogen homolog, formerly Antibody |
| Information: |
Target information shown above is from the UniProt Consortium. |
