|CD87||PLAUR (plasminogen activator, urokinase receptor), uPAR (urokinase plasminogen activator receptor)|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
|32 / 32|
35 / 35
66 / 66
68 / 68
|CD87 is expressed on T and NK cells, monocytes and neutrophils as well as non-hematopoietic cells that include vascular endothelial cells, fibroblasts, smooth muscle cells, keratinocytes, placental, trophoblasts, hepatocytes and a wide variety of tumor cells including breast, colon and prostate carcinoma melanoma. Among leukocytes, constitutive expression is weak or absent but exposure to soluble activating factors like LPS in monocytes and IL-2 in T-lymphocytes induces heightened message and cell surface expression. Upregulation of CD87 is correlated with the expression of CD25 on T cells. T cells from patients with viral infections are found to express high levels of CD87. In the case of neutrophils, activating stimuli trigger an increase in surface CD87 expression by the exocytosis of pre-formed CD87 on cytoplasmic granular membranes. |
|MOLECULAR FAMILY NAME: Belongs to the Ly6 superfamily. |
CD87 is a single-chain GPI-anchored 283 aa glycoprotein. It contains a 22 aa signal sequence, an extracellular domain which contains 3 uPAR/Ly6 homologous domains (DI, DII and DIII), a N-terminal domain and 5 N-glycosylation sites but lacks a transmembrane and a cytoplasmic domain and may be anchored to the plasma membrane by a GPI moiety following cleavage of the nascent polypeptide near its carboxy-terminus. Each uPAR/Ly6 domain consists of approximately 90 aa with 3-4 disulphide bonds and adopts a three finger fold with 3 adjacent loops rich in β-pleated sheets and a small C-terminal loop. Domains DI and DII have a folding topology similar to an α-neurotoxin, whereas DIII resembles CD59. All 3 uPAR/Ly6 domains are arranged in an almost circular fashion which generates a deep central cavity where urokinase plasminogen activator (uPA) can bind but the binding does not interfer with binding of ligands to the external receptor surface of CD87, enabling CD87 to be a multimer receptor. A cDNA lacking exon 5 has been reported.
Alternative splicing yields 3 different isoforms. cDNAs coding for truncated forms of human CD87 have been isolated which are generated by alternative mRNA splicing and code for putative soluble and secreted uPA binding proteins not yet found in nature.
Post-translational events include a cleavage step such that the carboxyl-terminal part of the sequence becomes bound to the glycolipid moiety. There are 5 N-glycosylation sites, 2 each on domains 2 and 3, and 1 on domain 1. Domain 1 can be cleaved by plasmin and chymotrypsin.
|CD87 binds urokinase plasminogen activation, vitronectin, β1 and β2 integrins and kininogen. The ligand for CD87 is uPA. CD87 has been shown to associate on monocytes with CD11a/CD18, CD11b/CD18 and Src-related kinases. Its association with CD11b/CD18 has also been demonstrated on resting neutrophils.|
LIGANDS AND MOLECULES ASSOCIATED WITH CD87
CD87 may form a functional linkage with members of the b1, b2 and b 3 integrin families, which may then serve as signaling partners. CD87 may also associate with other proteins that have tyrosine kinase activity.
|CD87 is a key molecule in the regulation of cell-surface plasminogen activation and plays an important role in many normal as well as pathologic processes. CD87 is the receptor for uPA, a serine protease that converts plasminogen to plasmin, which is then bound to physically adjacent plasma membrane receptors. Receptors for uPA and plasmin have been localized to the leading edge of migrating leukocytes and tumor cells indicating a co-operative interaction whereby the enzymatic activity of plasmin which is dependent upon the action of uPA causes the pericellular hydrolysis of extra-cellular matrix proteins in the path of cellular invasion. Knockout mice show a defect in CD87 mediated plasminogen activation. |
CD87 serves as the cellular receptor for pro-uPA and uPA.
DISEASE RELEVANCE AND FUNCTION OF CD87 IN INTACT ANIMAL
CD87 assists in the controlled extracellular matrix degradation following by intravasation and metastasis in various carcinomas and is thought to contribute to the process of neoplastic and inflammatory cell invasion. Thus, uPAR expression and the content of bound uPA have been implicated in the processes of inflammatory cell invasion and tumor cell metastasis. In the setting of certain cancers, high levels of uPAR expression or uPA content have been associated with a poor prognosis. In tumor cells and smooth muscle cells CD87 associates with CD130 and activates CD130 associated signaling components JAK1 and STAT1. CD87 may also contribute to b2 integrin-dependent adherence and cell chemotaxis but patients with LAD (lacking β2 integrin function) show CD87 signaling deficits.
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD87: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD87: No information.
The full range of CD87 functions remains to be explored, as is the mechanism by which it signals.
Database accession numbers
Revised June 25, 2008