CSF1R
GeneName
CSF1R
Summary
CSF1R, also known as FMS or CSF-1R, is a 108kDa receptor tyrosine kinase predominantly expressed on the surface of macrophages, monocytes, and certain neuronal cells. It is localised to the plasma membrane and plays a pivotal role in mediating responses to its ligand, macrophage colony-stimulating factor (CSF-1). CSF1R is involved in various biological processes including macrophage differentiation, cell migration, and inflammatory responses, and functions through signalling pathways that regulate cell proliferation and survival. The receptor forms complexes with other proteins and is crucial for maintaining cell-cell junctions and facilitating communication between cells in the immune system and nervous system.
Importance
CSF1R is relevant to: - The regulation of macrophage function and differentiation, impacting innate immunity and inflammation - Neuroinflammation and neurodegenerative diseases due to its role in microglial cell proliferation and function - Cancer biology as it can influence tumour microenvironments and macrophage-tumour interactions - Bone metabolism through its involvement in osteoclast differentiation and regulation of bone resorption
Top Products
For researchers investigating CSF1R, we recommend two excellent primary antibodies. The first is the well-cited polyclonal antibody, Anti-CSF-1-R antibody (ab215441), which is particularly effective for flow cytometry (FC) and has garnered 5 citations, reflecting its reliability in the field. Additionally, we offer the recombinant antibody, Anti-CSF-1-R antibody [EPR20754] (ab229188), which has been validated for a broader range of applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), and immunoprecipitation (IP). This recombinant product, with 4 citations, ensures batch-to-batch consistency, making it an excellent choice for researchers seeking dependable CSF1R detection across various experimental setups. The Anti-CSF-1-R antibody ELISA Kit (ab239079) is an excellent option for researchers looking to measure CSF1R in their experiments.
Abcam Product Citation Summary
The data indicates that the CSF1R target is being investigated in the context of human liver cancer, utilising both Western blotting and immunohistochemistry techniques. This suggests a focus on understanding the role of CSF1R in liver cancer pathology.
Abcam Product Citation Table
Domain
The juxtamembrane domain functions as autoinhibitory region. Phosphorylation of tyrosine residues in this region leads to a conformation change and activation of the kinase.
The activation loop plays an important role in the regulation of kinase activity. Phosphorylation of tyrosine residues in this region leads to a conformation change and activation of the kinase.
Function
Tyrosine-protein kinase that acts as a 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 pro-inflammatory 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, including the ERK1/2 and the JNK pathway (PubMed:20504948, PubMed:30982609). 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. In the central nervous system, may play a role in the development of microglia macrophages (PubMed:30982608).
Involvement in disease
Aberrant expression of CSF1 or CSF1R can promote cancer cell proliferation, invasion and formation of metastases. Overexpression of CSF1 or CSF1R is observed in a significant percentage of breast, ovarian, prostate, and endometrial cancers.
Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.
Leukoencephalopathy, hereditary diffuse, with spheroids 1
HDLS1
An autosomal dominant adult-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.
None
The disease is caused by variants affecting the gene represented in this entry.
Brain abnormalities, neurodegeneration, and dysosteosclerosis
BANDDOS
An autosomal recessive disease with variable manifestations. Main features are brain malformations with calcifying leukoencephalopathy, progressive neurodegeneration, and bone sclerotic features. The age at onset ranges from infancy to early adulthood. Neurologic features include loss of previous motor and language skills, cognitive impairment, spasticity, and focal seizures. Brain imaging shows periventricular white matter abnormalities and calcifications, large cisterna magna or Dandy-Walker malformation, and sometimes agenesis of the corpus callosum.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Autophosphorylated in response to CSF1 or IL34 binding (PubMed:20489731, PubMed:23408870, PubMed:24336230). 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.
Ubiquitinated. Becomes rapidly polyubiquitinated after autophosphorylation, leading to its degradation.
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.
Tissue Specificity
Expressed in bone marrow and in differentiated blood mononuclear cells.
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
Alternative names
CD115, FMS, CSF1R, Macrophage colony-stimulating factor 1 receptor, CSF-1 receptor, Proto-oncogene c-Fms, CSF-1-R, CSF-1R, M-CSF-R
Database links
swissprot:P07333 omim:164770 entrezGene:1436
Other research areas
- Immunology & Infectious Disease
- Neuroscience