Recombinant Human Macrophage colony-stimulating factor 1 receptor (CSF1R), partial

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)

Subcellular Location

Cell membrane (Single-pass type I membrane protein)

Disease Association

[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. [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. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed in bone marrow and in differentiated blood mononuclear cells

Subunit

Interacts with INPPL1/SHIP2 and THOC5 (By similarity). Monomer. Homodimer. Interacts with CSF1 and IL34. Interaction with dimeric CSF1 or IL34 leads to receptor homodimerization. Interacts (tyrosine phosphorylated) with PLCG2 (via SH2 domain). Interacts (tyrosine phosphorylated) with PIK3R1 (via SH2 domain). Interacts (tyrosine phosphorylated) with FYN, YES1 and SRC (via SH2 domain). Interacts (tyrosine phosphorylated) with CBL, GRB2 and SLA2

• Hampe A. et al. Nucleotide sequence and structural organization of the human FMS proto-oncogene. — Oncogene Res. (1989)
• Coussens L. et al. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. — Nature (1986)
• Andre C. et al. Sequence analysis of two genomic regions containing the KIT and the FMS receptor tyrosine kinase genes. — Genomics (1997)
• Jin P. et al. Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. — Arthritis Res. Ther. (2008)
• Schmutz J. et al. The DNA sequence and comparative analysis of human chromosome 5. — Nature (2004)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Visvader J. et al. Differential transcription of exon 1 of the human c-fms gene in placental trophoblasts and monocytes. — Mol. Cell. Biol. (1989)