Colony stimulating factor 1 receptor
Encyclopedia
Colony stimulating factor 1 receptor (CSF1R), also known as macrophage colony-stimulating factor receptor (M-CSFR), and CD115 (Cluster of Differentiation 115), is a cell-surface protein
encoded, in humans, by the CSF1R gene
. It is a receptor
for a cytokine
called colony stimulating factor 1
.
, a cytokine which controls the production, differentiation, and function of macrophage
s. This receptor mediates most, if not all, of the biological effects of this cytokine. Ligand
binding activates CSFR1 through a process of oligomer
ization and trans
phosphorylation
. The encoded protein is a tyrosine kinase
transmembrane receptor and member of the CSF1/PDGF receptor family of tyrosine-protein kinases. The first intron
of the CSFR1 gene contains a transcriptionally
inactive ribosomal protein L7
processed pseudogene
, oriented in the opposite direction to the CSFR1 gene.
and type M4 acute myeloblastic leukemia
. Increased levels of CSF1R1 are found in microglia
in Alzheimer's disease
and after brain injuries. The increased receptor expression causes microglia to become more active.
Both CSF1R, and its ligand colony stimulating factor 1
play an important role in the development of the mammary gland
and may be involved in the process of mammary gland carcinogenesis
.
with FYN
, Suppressor of cytokine signaling 1
, Grb2
and Cbl gene
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
encoded, in humans, by the CSF1R gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. It is a receptor
Immune receptor
An immune receptor is a receptor, usually on a cell membrane, which binds to a substance and causes a response in the immune system.-Types:...
for a cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
called colony stimulating factor 1
Macrophage colony-stimulating factor
Macrophage colony-stimulating factor, or M-CSF, is a secreted cytokine which influences hematopoietic stem cells to differentiate into macrophages or other related cell types. Eukaryotic cells also produce M-CSF in order to combat intercellular viral infection. M-CSF binds to the Colony...
.
Function
The protein encoded by the CSFR1 gene is the receptor for colony stimulating factor 1Macrophage colony-stimulating factor
Macrophage colony-stimulating factor, or M-CSF, is a secreted cytokine which influences hematopoietic stem cells to differentiate into macrophages or other related cell types. Eukaryotic cells also produce M-CSF in order to combat intercellular viral infection. M-CSF binds to the Colony...
, a cytokine which controls the production, differentiation, and function of macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s. This receptor mediates most, if not all, of the biological effects of this cytokine. Ligand
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
binding activates CSFR1 through a process of oligomer
Oligomer
In chemistry, an oligomer is a molecule that consists of a few monomer units , in contrast to a polymer that, at least in principle, consists of an unlimited number of monomers. Dimers, trimers, and tetramers are oligomers. Many oils are oligomeric, such as liquid paraffin...
ization and trans
Trans
Trans is a Latin noun or prefix, meaning "across", "beyond" or "on the opposite side".Trans may refer to:- Science and technology :* Cis-trans isomerism, in chemistry, a form of stereoisomerism...
phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
. The encoded protein is a tyrosine kinase
Receptor tyrosine kinase
Receptor tyrosine kinases s are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins....
transmembrane receptor and member of the CSF1/PDGF receptor family of tyrosine-protein kinases. The first intron
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
of the CSFR1 gene contains a transcriptionally
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
inactive ribosomal protein L7
RPL7
60S ribosomal protein L7 is a protein that in humans is encoded by the RPL7 gene.-Further reading:...
processed pseudogene
Pseudogene
Pseudogenes are dysfunctional relatives of known genes that have lost their protein-coding ability or are otherwise no longer expressed in the cell...
, oriented in the opposite direction to the CSFR1 gene.
Clinical significance
Mutations in CSF1R are associated with chronic myelomonocytic leukemiaChronic myelomonocytic leukemia
Chronic myelomonocytic leukemia is a form of leukemia featuring monocytosis.The categorization of this disease has been controversial. Patients with CMML can present with various clinical features, mimicking either myelodysplastic syndroms or myeloproliferative neoplasms depending upon a patient's...
and type M4 acute myeloblastic leukemia
Acute myeloblastic leukemia
Acute myeloblastic leukemia is a form of myeloid leukemia affecting myeloblasts.More specifically, it can refer to:* Minimally differentiated acute myeloblastic leukemia - * Acute myeloblastic leukemia without maturation -...
. Increased levels of CSF1R1 are found in microglia
Microglia
Microglia are a type of glial cell that are the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defense in the central nervous system . Microglia constitute 20% of the total glial cell population within the brain...
in Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
and after brain injuries. The increased receptor expression causes microglia to become more active.
Both CSF1R, and its ligand colony stimulating factor 1
Macrophage colony-stimulating factor
Macrophage colony-stimulating factor, or M-CSF, is a secreted cytokine which influences hematopoietic stem cells to differentiate into macrophages or other related cell types. Eukaryotic cells also produce M-CSF in order to combat intercellular viral infection. M-CSF binds to the Colony...
play an important role in the development of the mammary gland
Mammary gland
A mammary gland is an organ in mammals that produces milk to feed young offspring. Mammals get their name from the word "mammary". In ruminants such as cows, goats, and deer, the mammary glands are contained in their udders...
and may be involved in the process of mammary gland carcinogenesis
Carcinogenesis
Carcinogenesis or oncogenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells...
.
Interactions
Colony stimulating factor 1 receptor has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with FYN
FYN
Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth...
, Suppressor of cytokine signaling 1
Suppressor of cytokine signaling 1
Suppressor of cytokine signaling 1 is a protein that in humans is encoded by the SOCS1 gene. SOCS1 orthologs have been identified in several mammals for which complete genome data are available.-Interactions:...
, Grb2
Grb2
Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene....
and Cbl gene
Cbl gene
Cbl is a mammalian gene encoding several proteins including E3 ubiquitin-protein ligase CBL involved in cell signalling and protein ubiquitination...
.