View source for CD14

{{Short description|Mammalian protein found in humans}}
{{Infobox_gene}}
'''CD14''' ([[cluster of differentiation]] 14) is a human [[protein]] made mostly by [[macrophages]] as part of the [[innate immune system]].<ref name="pmid2472171">{{cite journal | vauthors = Setoguchi M, Nasu N, Yoshida S, Higuchi Y, Akizuki S, Yamamoto S | title = Mouse and human CD14 (myeloid cell-specific leucine-rich glycoprotein) primary structure deduced from cDNA clones | journal = Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression | volume = 1008 | issue = 2 | pages = 213–222 | date = July 1989 | pmid = 2472171 | doi = 10.1016/0167-4781(80)90012-3 }}</ref><ref name="pmid2462937">{{cite journal | vauthors = Simmons DL, Tan S, Tenen DG, Nicholson-Weller A, Seed B | title = Monocyte antigen CD14 is a phospholipid anchored membrane protein | journal = Blood | volume = 73 | issue = 1 | pages = 284–289 | date = January 1989 | pmid = 2462937 | doi = 10.1182/blood.V73.1.284.284 | doi-access = free }}</ref> It helps to detect bacteria in the body by binding [[lipopolysaccharide]] (LPS), a [[pathogen-associated molecular pattern]] (PAMP).

CD14 exists in two forms, one anchored to the membrane by a [[glycosylphosphatidylinositol]] (GPI) tail (mCD14), the other a soluble form (sCD14). Soluble CD14 either appears after shedding of mCD14 (48 [[kDa]]) or is directly secreted from intracellular vesicles (56 kDa).<ref name="pmid9575549">{{cite journal | vauthors = Kirkland TN, Viriyakosol S | title = Structure-function analysis of soluble and membrane-bound CD14 | journal = Progress in Clinical and Biological Research | volume = 397 | pages = 79–87 | year = 1998 | pmid = 9575549 }}</ref>

The x-ray crystal structure of human CD14 reveals a monomeric, bent solenoid structure containing a hydrophobic amino-terminal pocket.<ref name="pmid23264655">{{cite journal | vauthors = Kelley SL, Lukk T, Nair SK, Tapping RI | title = The crystal structure of human soluble CD14 reveals a bent solenoid with a hydrophobic amino-terminal pocket | journal = Journal of Immunology | volume = 190 | issue = 3 | pages = 1304–1311 | date = February 2013 | pmid = 23264655 | pmc = 3552104 | doi = 10.4049/jimmunol.1202446 }}</ref>

CD14 was the first described [[pattern recognition receptor]]<!-- The page for CRP (http://en.wikipedia.org/wiki/C-reactive_protein) says that CRP was the first PRR to be identified. Which is it? -->.

== Function ==
CD14 acts as a co-receptor (along with the [[Toll-like receptor]] [[TLR 4]] and [[Ly96|MD-2]]) for the detection of bacterial [[lipopolysaccharide]] (LPS).<ref name="pmid10608082">{{cite journal | vauthors = Kitchens RL | title = Role of CD14 in cellular recognition of bacterial lipopolysaccharides | journal = Chemical Immunology | volume = 74 | pages = 61–82 | year = 2000 | pmid = 10608082 | doi = 10.1159/000058750 | isbn = 3-8055-6917-3 | series = Chemical Immunology and Allergy }}</ref><ref name="pmid10608084">{{cite journal | vauthors = Tapping RI, Tobias PS | title = Soluble CD14-mediated cellular responses to lipopolysaccharide | journal = Chemical Immunology | volume = 74 | pages = 108–121 | year = 2000 | pmid = 10608084 | doi = 10.1159/000058751 | isbn = 3-8055-6917-3 | series = Chemical Immunology and Allergy }}</ref> CD14 can bind LPS only in the presence of [[lipopolysaccharide-binding protein]] (LBP).
Although LPS is considered its main [[ligand]], CD14 also recognizes other pathogen-associated molecular patterns such as lipoteichoic acid.<ref name="pmid23430250">{{cite journal | vauthors = Ranoa DR, Kelley SL, Tapping RI | title = Human lipopolysaccharide-binding protein (LBP) and CD14 independently deliver triacylated lipoproteins to Toll-like receptor 1 (TLR1) and TLR2 and enhance formation of the ternary signaling complex | journal = The Journal of Biological Chemistry | volume = 288 | issue = 14 | pages = 9729–9741 | date = April 2013 | pmid = 23430250 | pmc = 3617275 | doi = 10.1074/jbc.M113.453266 | doi-access = free }}</ref> Cluster of differentiation CD14 is a
receptor for a very wide range of microbial products including lipopolysaccharide (released from Gram-negative bacteria), peptidoglycans, and lipoteichoic acid (constituents of Gram-positive bacteria).<ref name="pmid15614125">{{cite journal | vauthors = De Maio A, Torres MB, Reeves RH | title = Genetic determinants influencing the response to injury, inflammation, and sepsis | journal = Shock | volume = 23 | issue = 1 | pages = 11–17 | date = January 2005 | pmid = 15614125 | doi = 10.1097/01.shk.0000144134.03598.c5 | s2cid = 35306289 | doi-access = free }}</ref>

[[Image:Toll-like receptor pathways revised.jpg|thumbnail|left|500px|Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations]]
{{Clear}}

==Tissue distribution==
CD14 is expressed mainly by [[macrophages]] and (at 10-times lesser extent) by [[neutrophil]]s. It is also expressed by [[dendritic cells]]. The soluble form of the receptor (sCD14) is secreted by the [[liver]] and [[monocyte]]s and is sufficient in low concentrations to confer LPS-responsiveness to cells not expressing CD14. mCD14 and sCD14 are also present on enterocytes.<ref name="pmid11349042">{{cite journal | vauthors = Funda DP, Tucková L, Farré MA, Iwase T, Moro I, Tlaskalová-Hogenová H | title = CD14 is expressed and released as soluble CD14 by human intestinal epithelial cells in vitro: lipopolysaccharide activation of epithelial cells revisited | journal = Infection and Immunity | volume = 69 | issue = 6 | pages = 3772–3781 | date = June 2001 | pmid = 11349042 | pmc = 98389 | doi = 10.1128/IAI.69.6.3772-3781.2001 }}</ref> sCD14 is also present in [[breast milk|human milk]], where it is believed to regulate microbial growth in the infant gut.

==Differentiation==
CD14+ [[monocytes]]  can differentiate into a host of different cells, including [[dendritic cell]]s, a differentiation pathway encouraged by [[cytokines]], including [[GM-CSF]] and [[Interleukin-4|IL-4]].

== Interactions ==

CD14 has been shown to [[Protein-protein interaction|interact]] with lipopolysaccharide-binding protein.<ref name=pmid12417309>{{cite journal | vauthors = Thomas CJ, Kapoor M, Sharma S, Bausinger H, Zyilan U, Lipsker D, Hanau D, Surolia A | display-authors = 6 | title = Evidence of a trimolecular complex involving LPS, LPS binding protein and soluble CD14 as an effector of LPS response | journal = FEBS Letters | volume = 531 | issue = 2 | pages = 184–188 | date = November 2002 | pmid = 12417309 | doi = 10.1016/S0014-5793(02)03499-3 | s2cid = 25135963 }}</ref><ref name=pmid7583357>{{cite journal | vauthors = Yu B, Wright SD | title = LPS-dependent interaction of Mac-2-binding protein with immobilized CD14 | journal = Journal of Inflammation | volume = 45 | issue = 2 | pages = 115–125 | year = 1995 | pmid = 7583357 }}</ref>

== References ==
{{Reflist|2}}

== External links ==
* {{UCSC gene info|CD14}}
* {{PDBe-KB2|P08571|Monocyte differentiation antigen CD14}}
* {{MeshName|CD14+Antigens}}

{{Clusters of differentiation}}
{{Clusters of differentiation by lineage}}
{{TLR signaling pathway}}

{{DEFAULTSORT:Cd14}}
[[Category:Clusters of differentiation]]