Granulocyte colony-stimulating factor receptor
Encyclopedia
The granulocyte colony-stimulating factor receptor (G-CSF-R) also known as CD114 (Cluster of Differentiation 114) is a protein
that in humans is encoded by the CSF3R gene
. G-CSF-R is a cell
-surface receptor
for the granulocyte colony-stimulating factor
(G-CSF). The G-CSF receptors belongs to a family of cytokine
receptors known as the hematopoietin
receptor family.The granulocyte colony-stimulating factor receptor is present on precursor cells in the bone marrow
, and, in response to stimulation by G-CSF, initiates cell proliferation and differentiation
into mature neutrophilic granulocytes and macrophages.
The G-CSF-R is a transmembrane receptor that consists of an extracellular ligand-binding portion, a transmembrane domain
, and the cytoplasmic portion that is responsible for signal transduction
. GCSF-R ligand-binding is associated with dimerization
of the receptor and signal transduction through proteins including Jak
, Lyn, STAT
, and Erk1/2
.
, also known as severe congenital neutropenia
.
Mutation
s in the intracellular part of this receptor are also associated with certain types of leukemia
.
In clinical medicine, there is a suggestion that use of GCSF
should be avoided, at least in children and adolescents and perhaps adults, when G-CSFR isoform IV is overexpressed.
with Grb2
, HCK
and SHC1
.
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...
that in humans is encoded by the CSF3R 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...
. G-CSF-R is a cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
-surface receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
for the granulocyte colony-stimulating factor
Granulocyte colony-stimulating factor
Granulocyte colony-stimulating factor is a colony-stimulating factor hormone. G-CSF is also known as colony-stimulating factor 3 ....
(G-CSF). The G-CSF receptors belongs to a family of 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...
receptors known as the hematopoietin
Erythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
receptor family.The granulocyte colony-stimulating factor receptor is present on precursor cells in the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, and, in response to stimulation by G-CSF, initiates cell proliferation and differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
into mature neutrophilic granulocytes and macrophages.
The G-CSF-R is a transmembrane receptor that consists of an extracellular ligand-binding portion, a transmembrane domain
Transmembrane protein
A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
, and the cytoplasmic portion that is responsible for signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
. GCSF-R ligand-binding is associated with dimerization
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
of the receptor and signal transduction through proteins including Jak
Jak
Jak may refer to:*JAK, Jazakomu Allahu Khayran *JAK members bank, a Swedish interest-free bank*Janus kinase, an intracellular signaling molecule; component of the JAK-STAT signal system...
, Lyn, STAT
STAT protein
The STAT protein regulates many aspects of growth, survival and differentiation in cells...
, and Erk1/2
Extracellular signal-regulated kinases
In molecular biology, extracellular-signal-regulated kinases or classical MAP kinases are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells...
.
Clinical significance
Mutations in this gene are a cause of Kostmann syndromeKostmann syndrome
Kostmann syndrome, also known as severe congenital neutropenia, autosomal recessive type 3 and Kostmann disease, is a rare autosomal recessive form of severe chronic neutropenia usually detected soon after birth...
, also known as severe congenital neutropenia
Neutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
.
Mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s in the intracellular part of this receptor are also associated with certain types of leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
.
In clinical medicine, there is a suggestion that use of GCSF
Granulocyte colony-stimulating factor
Granulocyte colony-stimulating factor is a colony-stimulating factor hormone. G-CSF is also known as colony-stimulating factor 3 ....
should be avoided, at least in children and adolescents and perhaps adults, when G-CSFR isoform IV is overexpressed.
Interactions
Granulocyte colony-stimulating factor 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 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....
, HCK
HCK
Tyrosine-protein kinase HCK is an enzyme that in humans is encoded by the HCK gene.-Interactions:HCK has been shown to interact with BCR gene, ELMO1, Cbl gene, RAS p21 protein activator 1, RASA3, Granulocyte colony-stimulating factor receptor, ADAM15 and RAPGEF1.-Further reading:...
and SHC1
SHC1
SHC-transforming protein 1 is a protein that in humans is encoded by the SHC1 gene. SHC has been found to be important in the regulation of apoptosis and drug resistance in mammalian cells....
.