|CD114||CSF3R (colony stimulating factor 3 receptor), HG-CSFR, G-CSFR (granulocyte colony stimulating factor receptor)|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
|130 / 130|
150 / 150
|CD114 is expressed during all stages of granulocyte differentiation, on neutrophils, monocytes, dendritic cells and mature platelets at different levels, on several nonhematopoietic cell types/tissues including endothelial cells, placenta, trophoblastic cells and many cultured tumor cell lines but is not found on eosinophilic granulocytes, lymphocytes and red cells.|
|MOLECULAR FAMILY NAME: Belongs to the cytokine receptor class 1 gene family.|
CD114 is a single-chain type-1 812 aaglycoprotein. It contains a 603 aa extracellular
domain which contains an Ig-like C2-type domain, 4 fibronectin type-3 repeats, (the second containing a WSXWS motif), and 9 potential N-glycosylation sites, a 26 aa transmembrane domain and an 183 aa intracellular cytoplasmic domain which has no intrinsic kinase activity.
Alternative splicing yields 6 different isoforms, one of which is a secreted soluble isoform. Splicing of exon 17 results in a receptor protein which is demonstrated in placenta and trophoblast cells and elongated by 27 aa. There are 4 other splice variants of exon 17 that were described in granulocytes and AML blasts. Alternative splicing of exon 15 yields a secreted, soluble form of the granulocyte colony-stimulating factor receptor (G-CSFR) as demonstrated in U937 cell line.
There is extensive N-glycosylation in the extracellular domain of 30 kDa-60 kDa and 9 potential N-glycosylation sites.
|A single class of high affinity binding sites for G-CSF, kDa = 100-500 pM, is detected on the cell surface. The monomeric form of purified murine CD114 binds G-CSF with a low affinity while its oligomeric forms show a high affinity binding, which suggests that the high affinity receptor may be formed by a homodimer of the CD114 protein. Following the binding of G-CSF to CD114, the Janus family Tyr kinases Jak1 and Jak2 and the transcriptional activator Stat3 are Tyr phosphorylated. Mutational analysis has shown that the cytokine receptor domain and the WSXWS motif are necessary for G-CSF binding and that a region of the cytoplasmic domain is essential for signal transduction. |
LIGANDS AND MOLECULES ASSOCIATED WITH CD114
|CD114 is the cytokine receptor for granulocyte colony stimulating factor (G-CSF) and is a regulator of myeloid differentiation and proliferation of neutrophils from their bone marrow precursors, activates mature neutrophils and causes proliferation and migration of endothelial cells. The receptor forms a homodimer when it binds ligand. After dimerization, signal transduction invoves the JAK-STAT pathway.|
CD114 is the receptor for G-CSF with a single binding affinity of kDa 200-500 pM.
DISEASE RELEVANCE AND FUNCTION OF CD114 IN INTACT ANIMAL
CD114 acts as a target for enhancing recovery of myelopoiesis in patients post chemotherapy, acts as a target for hematopoietic stem cell and progenitor cell mobilization for peripheral blood stem cell transplantation and as a target of G-CSF treatment in patients with severe chronic neutropenia, congenital, cyclic and idiopathic. G-CSF mutations were found in some patients with severe cogential neutropenia, known as Kostmann syndrome, and may be potentially involved in proliferation of myeloid leukemia cells.
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD114
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD114: No information.
Database accession numbers
Revised June 25, 2008