• Urokinase Plasminogen Activator Receptor, uPAR

MAJOR LINKS FOR CD87  

• NCBI LocusLink Record: 5329
• Mendelian Inheritance in Man (OMIM): 173391
• SwissProt annotated protein record: Q03405

• CD87 serves as the cellular receptor for pro-uPA and uPA

CELLULAR FUNCTION OF CD87  

• Receptor-bound uPA can convert 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 cooperative interaction whereby the enzymatic activity of plasmin (dependent upon the action of uPA) causes the pericellular hydrolysis of extra-cellular matrix proteins in the path of cellular invasion
• Thus, uPAR expression and the content of bound uPA have been implicated in the processes of inflammatory cell invasion and tumor cell metastasis
• CD87 may also contribute to beta2 integrin-dependent adherence and chemotaxis

DISEASE RELEVANCE OF CD87 AND FUNCTION OF CD87 IN INTACT ANIMAL  

• CD87 is thought to contribute to the process of neoplastic and inflammatory cell invasion
• In the setting of certain cancers, high levels of uPAR expression or uPA content have been associated with a poor prognosis

• Families in which CD87 is a member
  • CD87-->Glycosyl phosphatidyl inositol anchored

MOLECULAR STRUCTURE OF CD87  

• Single chain 283 amino acid GPI-anchored receptor with five N-glycosylation sites
• Consists of three homologous domains of approximately ninety amino acids
• N-terminal domain 1 (amino acids 1-92) plays a dominant role in ligand (uPA) binding

MOLECULAR MASS OF CD87  

POST-TRANSCRIPTIONAL MODIFICATION OF CD87  

• cDNAs coding for truncated forms of human CD87 have been isolated which are generated by alternative mRNA splicing and code for putative soluble, secreted uPA binding proteins (not as yet found in nature)

POST-TRANSLATIONAL MODIFICATION OF CD87  

• Human CD87 is encoded as a 313 amino acid residue polypeptide, excluding a 22 residue signal peptide
• Post-translational events include a cleavage step such that the carboxyl-terminal part of the sequence becomes bound to the glycolipid moiety
• There are five N-glycosylation sites, two each on domains 2 and 3, and one on domain 1
• Domain 1 can be cleaved by plasmin and chymotrypsin

SUBSTRATES FOR CD87   - No information

ENZYMES WHICH MODIFY CD87   - No information

LIGANDS FOR CD87 AND MOLECULES ASSOCIATED WITH CD87  

• CD87 may form a functional linkage with members of the b1, b2, and b3 integrin families, which may then serve as signaling partners
• CD87 may also associate with other proteins that have tyrosine kinase activity

• CD87 is expressed by T-cells, 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 (e.g., LPS in monocytes; IL-2 in T-lymphocytes) induces heightened message and cell surface expression
• 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

• The full range of CD87 functions remains to be explored, as is the mechanism by which it signals

SELECTION OF OTHER CD87-SPECIFIC REFERENCE MAB  

REVIEWS

1. Dano, K et al. 1994. Fibrinolysis 8: 189-203.

2. Petty HR,Todd RF 3d Integrins as promiscuous signal transduction devices. Immunol Today 1996 17:209 PubMed

3. Vassalli, J D. 1994. Fibrinolysis 8: 172-181.

PRIMARY CITATIONS

4. Gadd SJ,Majdic O,Kasinrerk W,Stockinger H,Maurer D,Eher R,Knapp W M5, a phosphoinositol-linked human myelomonocytic activation-associated antigen. Clin Exp Immunol 1990 80:252 PubMed

5. Gyetko MR,Sitrin RG,Fuller JA,Todd RF 3rd,Petty H,Standiford TJ Function of the urokinase receptor (CD87) in neutrophil chemotaxis. J Leukoc Biol 1995 58:533 PubMed

6. Luther T,Magdolen V,Albrecht S,Kasper M,Riemer C,Kessler H,Graeff H,Muller M,Schmitt M Epitope-mapped monoclonal antibodies as tools for functional and morphological analyses of the human urokinase receptor in tumor tissue. Am J Pathol 1997 150:1231 PubMed

7. Mizukami IF,Vinjamuri SD,Trochelman RD,Todd RF 3d A structural characterization of the Mo3 activation antigen expressed on the plasma membrane of human mononuclear phagocytes. J Immunol 1990 144:1841 PubMed

8. Schaefer BM,Stark HJ,Fusenig NE,Todd RF 3rd,Kramer MD Differential expression of urokinase-type plasminogen activator (uPA), its receptor (uPA-R), and inhibitor type-2 (PAI-2) during differentiation of keratinocytes in an organotypic coculture system. Exp Cell Res 1995 220:415 PubMed

9. Wei Y,Waltz DA,Rao N,Drummond RJ,Rosenberg S,Chapman HA Identification of the urokinase receptor as an adhesion receptor for vitronectin. J Biol Chem 1994 269:32380 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov