|CD14||LPS receptor (LPS-R)|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
|53 / 53|
55 / 55
|CD14 is expressed strongly on the surface of monocytes, osteoclast progenitors and macrophages and weaker on the surface of granulocytes, on tissue macrophages, Langerhans cells and microglia but not expressed by myeloid progenitors. It can be induce Rd with certain cytokines or fMLP. IFN-g or IL-13 treatment decreases expression on monocytes. In mice stimulated with lipopolysaccharide (LPS), CD14 expression is detected in non-myeloid cell types like hepatocytes and several epithelial cell types. Soluble forms can be detected in plasma serum and tissue culture supernatants of cells transfected with CD14. The antigen has also been detected, at low levels, on human B cells. The level of expression on granulocytes is higher in rabbits and goats than in other species that have been examined.|
|MOLECULAR FAMILY NAME: Belongs to the lipopolysaccharide receptor family.|
CD14 is a GPI-anchored 356 aa glycoprotein. It contains a 19aa signal peptide, an extracellular domain which contain 11 leucine-rich repeat (LRR) domains, 4 N-glycosylation sites and an unknown number of O-glycosylation sites. These LRR domains, however do not show the regular size or enough of the sequence patterns characteristic of LRR repeats to be included in this family. At least 2 soluble forms of CD14 have been described, one retains GPI and is released from the cell surface which results in an approximately 48 kDa molecule and the other i s released prior to the addition of the GPI anchor resulting in a higher molecular weight (>48 kDa). The CD14 gene contains a single 88 base pair intron immediately following the initiation condon and maps to a chromosome region with other genes encoding growth factors and receptor. In humans, this chromosomal region containing other genes encodes growth factors such as IL-3, IL-4, IL-5, IL-9, GM-CSF and receptors such as M-CSFR, PDGFR, a1 - and b2-adrenergic receptors. Soluble forms of CD14 are present in normal serum and urine of nephrotic patients and the culture media of cells expressing CD14.
POST-TRANSCRIPTIONAL MODIFICATION: No information.
CD14 is N-linked glycosylation and the GPI-anchor is at the C-terminus.
|CD14 is a receptor for the complex of LPS and the LPS-binding protein (LBP). The complex may be associated with the Toll-like receptor 2, depending on species.|
LIGANDS AND MOLECULES ASSOCIATED WITH CD14
Indirect studies suggest that CD14 may also bind lipoarabinomannan, peptidoglycan, and manuronic acids. While it is clear that peptidoglycan preparations stimulate cells in a CD14-dependent fashion, recent data suggest that a non-covalently linked hydrophobic contaminant of the peptidoglycan is the substance that binds CD14.
|CD14 functions as a receptor for endotoxin LPS and have been shown to bind apoptotic cells. LPS binds to a serum protein, LBP which facilitates the binding of LPS to CD14. When LPS binds to CD14 expressed on monocytes or neutrophils, the cells become activated and release cytokines such as TNF and upregulate cell suface molecules, including adhesion molecules. In vitro studies show that sCD14 can bind to LPS. The sCD14/LPS complex can then stimulate cells, which do not express membrane CD15 like endothelial cells and some epithelial cells. This stimulation occurs through an unidentified receptor to secrete cytokines and upregulate adhesion molecules. TNFa synthesis induced by LPS in monocytes and macrophages can be blocked by anti-CD14 mAbs. The interaction of CD14 with the LPS-LBP complex causes an increase in the adhesive activity of CD11b/CD18 CR3 on neutrophils. Transgenic mice overexpressing human CD14 show increased susceptibility to endotoxin shock, whereas CD14-deficient mice are highly resistant to either live gram-negative bacteria or LPS. CD14-deficient mice also show dramatically reduced levels of bacteremia following in vivo challenge with E. coli, suggesting a role for CD14 in dissemination of gram-negative bacteria.|
CD14 is a receptor for endotoxin LPS. Some studies suggest that sCD14 may act, in concert with LBP, as a lipid transfer molecule.
DISEASE RELEVANCE AND FUNCTION OF CD14 IN INTACT ANIMAL
CD14 is required for induction of cytokines and/or lethality in murine model of shock induced endotoxin or live E. coli 0111. Soluble forms of CD14 are found in plasma at a concentration of about 3 mg/ml. In whole blood, the amount of soluble CD14 exceeds the amount of membrane-bound CD14 by 2-3 logs. Deletions in the chromosomal region of CD14 are frequently found in myeloid leukemias
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD14: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD14
Database accession numbers
Revised June 25, 2008