CD50 ICAM-3 ( intercellular adhesion molecule-3)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Leukocyte
Blood Cell
Lymphoma Cell
Langerhans Cell
Lymphocyte
Neutrophil
Endothelial Cell
Dendritic Cell
110 / 110
170 / 170

Expression
CD50 is expressed at high levels on leukocytes of all lineages, epidermal Langerhans cells and endothelial cells but is generally absent from cells and tissues of nonhematopoietic origin.  CD50 has been detected on blood vessels within some lymphomas.  CD50 is released from activated lymphocytes and neutrophils, probably by proteolytic cleavage, and soluble forms of CD50 are detectable in the blood.


Structure
MOLECULAR FAMILY NAME:  Belongs to the immunoglobulin supergene family.

CD50 is a single-pass type-1 518 aa glycoprotein.  It  contains a 456 aa extracellular domain which contains 5 Ig-like C2-type domains and 15 potential glycosylation sites but only half are thought to be glycosylated at any one time, a 25 aa transmembrane domain and a 37 aa cytoplasmic domain that is tyrosine and serine phosphorylated in activated cells and is associated with tyrosine kinase activity.  The extracellular domains is proteolytically cleaved when leukocytes are activated and soluble forms are found in blood.  CD50 is structurally homologous to CD54 (ICAM-1) and CD102 (ICAM-2) and is a heavily and variably glycosylated glycoprotein.  Both proteins have 5 C2-set IgSF domains in their extracellular regions with a 52% identity.  The 2 membrane-distal IgSF domains of CD50 share ~37% identity with the extracellular portion of CD102 ICAM-2.  Electron microscopy studies suggest that CD50 is a straight rod approximately 15 nm in length. 

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
U937 120-140 kDa
HL60 120-140 kDa
SKW3 110-120 kDa
Jurkat 110-120 kDa
Neutrophils 115-135 kDa

POST-TRANSCIPTIONAL MODIFICATION

CD50 is phosphorylated by PKC.

POST-TRANSLATIONAL MODIFICATION

The CD50 cytoplasmic domain, which is poorly conserved in CD54 and CD102, is phosphorylated on tyrosine and serine residues following cell activation.



Ligands
CD50 has been shown to bind CD209 (DC-SIGN) as a receptor on dendritic cells.  CD50, like CD54 and CD102, is a ligand for the leukocyte integrin LFA-1 CD11a/CD18.  Residues on the GFC b-sheet of the N-terminal domain interact with CD11a I domain.  Optimal LFA-1 binding to CD50 as well as CD54 and CD102 requires activation of the cells expressing LFA-1.  Unlike CD54, CD50 does not bind the integrins CD11b/CD18 Mac-1 or CD11c/CD18 p150,95. Crosslinked CD50 antibodies co-precipitate the tyrosine kinases Fyn and Lck.

LIGANDS AND MOLECULES ASSOCIATED WITH CD50
Molecule Comment
CD11a/CD18 (LFA-1) LFA-1 cannot bind to CD50 without activation
Integrin a-d/b2 Integrin a-d/b2 binds CD50 constitutively without requiring activation




Function
CD50, a co-stimulatory molecule, regulates CD11a/CD18 (LFA-1)/CD54 (ICAM-1) and integrin-b1-dependent pathways adhesion.  It functions as an adhesion molecule during initial contact between T cell and antigen presenting cells prior to antigen recognition and is a potent signaling molecule.  CD50 provides a co-stimulatory signal during immune response that leads to polarization of the micotubular cytoskeleton.  CD50 mediates adhesion between leukocytes.  CD50 redistributes to leukocyte uropods during cell migration and plays a role in cell recruitment.  It is constitutively expressed on resting antigen-presenting cells, including dendritic cells, and appears to be important in the initial interaction between T and dendritic cells leading to T cell activation.  CD209 (DC-SIGN), a C-lectin expressed by dendritic cells, is a high affinity for dendritic cell-specific CD50 and may therefore play a role in primary immune responses.  Extensive crosslinking of CD50 on T cells with mAbs can mobilize intracellular Ca2+, activate tyrosine phosphorylation, and stimulate T cell adhesion and proliferation, but the functional significance of these observations is unclear. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD50 IN INTACT ANIMAL: No information.


Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD50

The elements are unidentified molecules 38 kDa, 70 kDa and 125 kDa.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD50

Upon TCR activation, CD50 becomes phosphorylated on serine residues in a transient manner.

ADDITIONAL INSIGHTS

CD50 regulates leukocyte morphology.  It redistributes to leukocyte uropods during cell chemotaxis and is involved in cell recruitment.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3385P32942
Antibodies
ICAM3.3   View Reactivity
KS128   View Reactivity
TU41   View Reactivity

Revised June 25, 2008


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